EP0000526A1 - Préparations pharmaceutiques qui contiennent des pénicillines ou céphaloporines et de l'acide clavulanique; procédé pour leur préparation - Google Patents

Préparations pharmaceutiques qui contiennent des pénicillines ou céphaloporines et de l'acide clavulanique; procédé pour leur préparation Download PDF

Info

Publication number
EP0000526A1
EP0000526A1 EP78100407A EP78100407A EP0000526A1 EP 0000526 A1 EP0000526 A1 EP 0000526A1 EP 78100407 A EP78100407 A EP 78100407A EP 78100407 A EP78100407 A EP 78100407A EP 0000526 A1 EP0000526 A1 EP 0000526A1
Authority
EP
European Patent Office
Prior art keywords
carbonylamino
oxo
imidazolidin
acid
see diagramm
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP78100407A
Other languages
German (de)
English (en)
Other versions
EP0000526B1 (fr
Inventor
Karl Georg Dr. Metzger
Hans-Bodo Dr. König
Wilfried Dr. Schröck
Michael Dr. Preiss
Peter Dr. Feyen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer AG
Original Assignee
Bayer AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Bayer AG filed Critical Bayer AG
Publication of EP0000526A1 publication Critical patent/EP0000526A1/fr
Application granted granted Critical
Publication of EP0000526B1 publication Critical patent/EP0000526B1/fr
Expired legal-status Critical Current

Links

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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M2201/00—Inorganic compounds or elements as ingredients in lubricant compositions
    • C10M2201/02—Water
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M2209/00—Organic macromolecular compounds containing oxygen as ingredients in lubricant compositions
    • C10M2209/10—Macromolecular compoundss obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • C10M2209/103—Polyethers, i.e. containing di- or higher polyoxyalkylene groups
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M2209/00—Organic macromolecular compounds containing oxygen as ingredients in lubricant compositions
    • C10M2209/10—Macromolecular compoundss obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • C10M2209/103—Polyethers, i.e. containing di- or higher polyoxyalkylene groups
    • C10M2209/104—Polyethers, i.e. containing di- or higher polyoxyalkylene groups of alkylene oxides containing two carbon atoms only
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M2219/00—Organic non-macromolecular compounds containing sulfur, selenium or tellurium as ingredients in lubricant compositions
    • C10M2219/04—Organic non-macromolecular compounds containing sulfur, selenium or tellurium as ingredients in lubricant compositions containing sulfur-to-oxygen bonds, i.e. sulfones, sulfoxides
    • C10M2219/044—Sulfonic acids, Derivatives thereof, e.g. neutral salts
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10N—INDEXING SCHEME ASSOCIATED WITH SUBCLASS C10M RELATING TO LUBRICATING COMPOSITIONS
    • C10N2020/00—Specified physical or chemical properties or characteristics, i.e. function, of component of lubricating compositions
    • C10N2020/01—Physico-chemical properties
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10N—INDEXING SCHEME ASSOCIATED WITH SUBCLASS C10M RELATING TO LUBRICATING COMPOSITIONS
    • C10N2040/00—Specified use or application for which the lubricating composition is intended
    • C10N2040/20—Metal working

Definitions

  • the present invention relates to new antibiotic synergistic active ingredient combinations of ⁇ -lactam antibiotics on the one hand and the clavulanic acid acting as a synergist or its pharmaceutically usable salts or esters, in particular its sodium salt, on the other hand.
  • clavulanic acid can have an inhibitory effect on ⁇ -lactamases. It is also known and experimentally proven that the minimum inhibitory concentrations of ampicillin, amoxicillin, carbenicillin and benzylpenicillin are significantly reduced by clavulanic acid as a synergist (see DT-OS 2 517 316, examples 42 and 44).
  • B-lactam antibiotics mentioned and their pharmaceutically acceptable salts are known [see, for example, DT-OS 2 104 588, DT-OS 2 152 967, DT-OS 2 525 541, DT-OS 2 525 541, 2 519 400, U.S. Patent 3,974,287.
  • Clavulanic acid as well as its pharmaceutically usable salts and in vivo cleavable esters are described in DT-OS 2 517 316.
  • the active ingredient combination according to the invention of D- ⁇ [(3-methylsulfonyl-2-oxoimidazolidin-1-yl) carbonylamino] benzylpenicillin with clavulanic acid with regard to its antibiotic activity of an active ingredient combination of ampicillin and clavulanic acid as described in DT-OS 2 517 316 is described as being particularly effective, is surprisingly superior, namely against E.coli F14, E.coli Weg, Klebsiella 1857 and Proteus morg. 932, about 3 times better, against E.coli T7, E.coli A 261 and Proteus vulg.
  • the antibacterial activity of the active ingredient combination according to the invention is significantly higher than the sum of the effects of the individual active ingredients. So there is a real synergistic effect.
  • the active ingredient combinations thus represent a valuable addition to the pharmaceutical industry.
  • the weight ratios of the active ingredients (1) and (2) can vary within relatively large ranges, namely from the ratio (1) to (2) such as 1 to 10 to the ratio (1) to (2) as 10 to 1.
  • the range (1) to (2) is preferably 1 to 5 to 5 to 1, very particularly preferably the range 1 to 3 to 3 to 1.
  • the invention further relates to medicaments containing an active ingredient combination consisting of a penicillin or cephalosporin of the general formula I or a pharmaceutically usable salt thereof and clavulanic acid or its pharmaceutically usable salts or esters.
  • the sodium salts are preferred.
  • esters of clavulanic acid the methyl and ethyl esters are preferred.
  • the present invention includes those pharmaceutical formulations that can be used parenterally, locally or orally.
  • Parenteral and oral, very particularly parenteral, forms of use are preferred.
  • the use forms preferably comprise sterile formulations suitable for injection or infusion purposes.
  • Mixtures of clavulanic acid or its salts or esters with the penicillins or cephalosporins mentioned, for example D- ⁇ [(3-methylsulfonyl-2-oxo-imidazolidin-1-yl) carbonylaminoJ-benzylpenicillin sodium, can be used in a formulated single dose per person , with a total amount of 0.5 to 10 g. About 0.5 g to 30 g of the active ingredient mixture can be administered per person on one day of treatment. However, this is not a restrictive information; because the single dose and the dosing intervals vary a lot with the severity of the infection.
  • medicaments according to the invention in addition to clavulanic acid or its esters or salts, e.g. B. their sodium salt, also several of the penicillins or cephalosporins mentioned, for. B. D- ⁇ - [(3-methylsulfonyl-2-oxo-imidazoli- din-1-yl) carbonylamino] benzylpenicillin sodium and D- ⁇ - [(imidazolidin-2-oxo-1-yl) carbonylamino] benzylpenicillin.
  • the pharmaceuticals according to the invention have a strong tolerance to a strong antimicrobial activity.
  • the pharmaceuticals according to the invention are active against a very broad spectrum of microorganisms. With their help e.g. Gram-negative and gram-positive bacteria and bacteria-like microorganisms are combated and the diseases caused by these pathogens are prevented, improved and / or cured.
  • the active substance mixtures according to the invention are particularly effective against bacteria and bacterial-like microorganisms. They are therefore particularly well suited for the prophylaxis and chemotherapy of local and systemic infections in human and veterinary medicine, which are caused by these pathogens.
  • Pasteurella bacteria e.g. Pasteurella multocida
  • Past.pseudotuberculosis Pasteurella
  • Haemophilus bacteria e.g. Haemophilus influenzae.
  • Bacteroidacea such as Bacteroides bacteria, e.g. Bacteroides fragilis.
  • the present invention includes pharmaceutical preparations which, in addition to non-toxic, inert pharmaceutically suitable excipients, clavulanic acid and one or more penicillins or cephalosporins according to the invention, and processes for the preparation of these preparations.
  • the present invention also includes pharmaceutical preparations in dosage units.
  • the preparations in the form of individual parts e.g. Tablets, dragees, capsules, pills, suppositories and ampoules are available, the active ingredient mixture of which corresponds to a fraction or a multiple of a single dose.
  • the dosage units can e.g. 1, 2, 3 or 4 single doses or 1/2, 1/3 or 1/4 of a single dose.
  • a single dose preferably receives the amount of active ingredient which is administered in one application and which usually corresponds to a whole, a half or a third or a quarter of a daily dose.
  • Non-toxic, inert pharmaceutically suitable excipients are to be understood as solid, semisolid or liquid diluents, fillers and formulation auxiliaries of all kinds.
  • the preferred pharmaceutical preparations are tablets, dragees, capsules, pills, granules, suppositories, solutions, suspensions and emulsions. Called slaben, gels, creams, lotions, powders and sprays.
  • Tablets, dragees, capsules, pills and granules can contain the active ingredient (s) in addition to the usual carriers, such as (a) fillers and extenders, e.g. Starches, milk sugar, cane sugar, glucose, mannitol and silica, (b) binders, e.g. Carboxymethyl cellulose, alginates, gelatin, folyvinyl pyrrolidone, (c) humectants, e.g. Glycerin, (d) disintegrant, e.g. Agar-agar, calcium carbonate and sodium bicarbonate, (e) solution retarders, e.g. Paraffin and (f) absorption accelerators, e.g.
  • fillers and extenders e.g. Starches, milk sugar, cane sugar, glucose, mannitol and silica
  • binders e.g. Carboxymethyl cellulose, alginates, gelatin, folyvinyl pyrrolidone
  • quaternary ammonium compounds (g) wetting agents, e.g. Catyl alcohol, glycerol monostearate, (h) adsorbent e.g. Kaolin and bentonite and (i) lubricants, e.g. Talc, calcium and magnesium stearate and solid polyethylene glycols or mixtures of the substances listed under (a) to (i).
  • wetting agents e.g. Catyl alcohol, glycerol monostearate
  • adsorbent e.g. Kaolin and bentonite
  • lubricants e.g. Talc, calcium and magnesium stearate and solid polyethylene glycols or mixtures of the substances listed under (a) to (i).
  • the tablets, dragees, capsules, pills and granules can be provided with the usual coatings and casings, optionally containing opacifying agents, and can also be composed such that they release the active ingredient (s) only or preferably in a certain part of the intestinal tract, optionally with a delay, where as embedding compounds, for example Foam substances and waxes can be used.
  • the active compound mixtures according to the invention can optionally also be in microencapsulated form with one or more of the above-mentioned carriers.
  • Supplitories can contain the usual water-soluble or water-insoluble carriers in addition to the active ingredient mixture, eg polyethylene glycols, fats, eg cocoa fats, and higher esters (eg C 14 alcohol with C 16 fatty acid) and mixtures of these substances.
  • the active ingredient mixture eg polyethylene glycols, fats, eg cocoa fats, and higher esters (eg C 14 alcohol with C 16 fatty acid) and mixtures of these substances.
  • ointments, pastes, creams and gels can contain the usual excipients, e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances.
  • excipients e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances.
  • Powders and sprays can contain the usual carriers, e.g. Milk sugar, talc, silica, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays can also use the usual propellants e.g. Chlorofluorocarbons included.
  • solutions and emulsions can contain the usual carriers such as solvents, solubilizers and emulsifiers, e.g. Water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, in particular cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerin, glycerol formate, fatty alcohol ester fatty acid, tetrahydrofuran desorbate or mixtures of these substances.
  • solvents e.g. Water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, in particular cottonseed oil
  • solutions and emulsions can also be in sterile and blood isotonic form.
  • suspensions can contain the usual carriers such as liquid diluents, for example water, ethyl alcohol, propylene glycol, suspending agents, for example ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and Contain sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar agar and tragacanth or mixtures or substances.
  • liquid diluents for example water, ethyl alcohol, propylene glycol
  • suspending agents for example ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and Contain sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar agar and tragacanth or mixtures or substances.
  • the formulation forms mentioned can also contain colorants, preservatives and odor and taste-improving additives, e.g. Peppermint oil and eucalyptus oil, and sweeteners z.3. Contain saccharin.
  • the therapeutically active combinations of active ingredients should be present in the pharmaceutical preparations listed above preferably in a concentration of about 0.1 to 99.5, preferably about 0.5 to 95 percent by weight of the total mixture.
  • the pharmaceutical preparations listed above can also contain other pharmaceutical active ingredients.
  • the pharmaceutical preparations listed above are prepared in a conventional manner by known methods, e.g. by mixing the active ingredient mixture with pharmaceutically usable carriers and additives.
  • the present invention also includes the use of the active substance mixtures according to the invention and of pharmaceutical preparations which contain two or more active substances according to the invention in human and veterinary medicine for preventing, ameliorating and / or curing the diseases mentioned above.
  • the active substance mixtures or the pharmaceutical preparations can be applied locally, orally, parenterally, intraperitoneally and / or rectally, preferably parenterally, in particular intravenously and intramuscularly.
  • the active compound mixture according to the invention in total amounts of about 1.5 to about 60, preferably 1.5 to 15 g / person per 24 hours, optionally in the form of several , e.g. of 3 single doses to achieve the desired results.
  • a single dose contains the active ingredient mixture (s) according to the invention preferably in amounts of about 0.1 to about 20 g, in particular 0.1 to 1.5 g / person.
  • the new active ingredient mixtures When used as a feed additive, the new active ingredient mixtures can be given in the usual way together with the feed or with feed preparations or with the drinking water. This prevents infection by gram-negative or gram-positive bacteria and also improves the utilization of the feed.
  • the new drug combinations are characterized by strong antibacterial effects, which have been tested in vivo and in vitro, and by oral resorbability.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP78100407A 1977-07-26 1978-07-17 Préparations pharmaceutiques qui contiennent des pénicillines ou céphaloporines et de l'acide clavulanique; procédé pour leur préparation Expired EP0000526B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19772733642 DE2733642A1 (de) 1977-07-26 1977-07-26 Antibiotische mittel
DE2733642 1977-07-26

Publications (2)

Publication Number Publication Date
EP0000526A1 true EP0000526A1 (fr) 1979-02-07
EP0000526B1 EP0000526B1 (fr) 1980-11-12

Family

ID=6014859

Family Applications (1)

Application Number Title Priority Date Filing Date
EP78100407A Expired EP0000526B1 (fr) 1977-07-26 1978-07-17 Préparations pharmaceutiques qui contiennent des pénicillines ou céphaloporines et de l'acide clavulanique; procédé pour leur préparation

Country Status (8)

Country Link
EP (1) EP0000526B1 (fr)
JP (1) JPS5435219A (fr)
AT (1) AT361618B (fr)
DE (2) DE2733642A1 (fr)
DK (1) DK330478A (fr)
ES (1) ES471984A1 (fr)
IL (1) IL55206A (fr)
IT (1) IT1097330B (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0008905A1 (fr) * 1978-09-06 1980-03-19 Beecham Group Plc Compositions pharmaceutiques contenant deux dérivés de bêta-lactame
EP0049968A1 (fr) * 1980-10-15 1982-04-21 Beecham Group Plc Compositions pharmaceutiques
EP0050253A1 (fr) * 1980-10-17 1982-04-28 Dr. Karl Thomae GmbH Composition pharmaceutique antibiotique
AT413015B (de) * 2001-04-12 2005-10-15 Sandoz Ag Tablette enthaltend das k-salz der 3-(2-hydroxyethyliden)-7-oxo-4-oxa-1- azabicyclo(3.2.0)heptan-2 carbonsäure in hydrophobisierter form

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59104319A (ja) * 1982-12-06 1984-06-16 Chugai Pharmaceut Co Ltd 抗菌剤およびそのキツト
JPS60146825A (ja) * 1984-01-10 1985-08-02 Asahi Chem Ind Co Ltd 経口医薬製剤

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2648770A1 (de) * 1975-10-31 1977-05-05 Beecham Group Ltd Penicillin-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2648770A1 (de) * 1975-10-31 1977-05-05 Beecham Group Ltd Penicillin-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0008905A1 (fr) * 1978-09-06 1980-03-19 Beecham Group Plc Compositions pharmaceutiques contenant deux dérivés de bêta-lactame
EP0049968A1 (fr) * 1980-10-15 1982-04-21 Beecham Group Plc Compositions pharmaceutiques
EP0050253A1 (fr) * 1980-10-17 1982-04-28 Dr. Karl Thomae GmbH Composition pharmaceutique antibiotique
AT413015B (de) * 2001-04-12 2005-10-15 Sandoz Ag Tablette enthaltend das k-salz der 3-(2-hydroxyethyliden)-7-oxo-4-oxa-1- azabicyclo(3.2.0)heptan-2 carbonsäure in hydrophobisierter form

Also Published As

Publication number Publication date
ATA534478A (de) 1980-08-15
IL55206A0 (en) 1978-09-29
IL55206A (en) 1981-12-31
DE2860275D1 (en) 1981-02-05
JPS5435219A (en) 1979-03-15
DE2733642A1 (de) 1979-02-08
DK330478A (da) 1979-03-02
EP0000526B1 (fr) 1980-11-12
IT7826041A0 (it) 1978-07-24
IT1097330B (it) 1985-08-31
AT361618B (de) 1981-03-25
ES471984A1 (es) 1979-10-16

Similar Documents

Publication Publication Date Title
DE2819479C2 (fr)
DE3019244C2 (fr)
EP0000526B1 (fr) Préparations pharmaceutiques qui contiennent des pénicillines ou céphaloporines et de l'acide clavulanique; procédé pour leur préparation
EP0247431B1 (fr) Antibiotiques du 6-hydroxyméthylcarbapénème substitués, leur procédé de préparation et leur application
EP0000380A1 (fr) Pénicillines, procédé pour leur préparation et leur application
DE2732283A1 (de) Beta-lactam-verbindungen
DE2354219A1 (de) Beta-lactam-antibiotica, ein verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
EP0003992A2 (fr) Composés bêta-lactame, procédé pour leur préparation et leur usage comme médicaments
CH639100A5 (de) Verfahren zur herstellung neuer beta-lactam antibiotika.
EP0092722B1 (fr) Antibiotiques bêta-lactamiques, procédé pour leur préparation ainsi que leur utilisation comme médicaments
DE3833693A1 (de) Stabile oxapenem-3-carbonsaeuren und ihre verwendung als ss-lactamasehemmer
EP0326887B1 (fr) Antibiotique de bêta-lactame, leur procédé de préparation er leur application comme et dans des médicaments
EP0268963A1 (fr) Antibiotiques du type benzazolylthiocarbapénème
DE2528079A1 (de) Penicilline, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
EP0101933A1 (fr) Dérivés de la 4 H-benzothiazine-1,4, leur procédé de préparation et leur application comme médicaments, additifs pour aliments des animaux et agents conservateurs
EP0000393A1 (fr) Composés bêta-lactames, procédé pour leur préparation et leur utilisation
EP0405217A1 (fr) 2-isocéphèmes et 2-oxa-isocéphèmes, procédé pour leur préparation et leur utilisation comme et dans des médicaments
EP0004590A1 (fr) Dérivés de pénicilline et de céphalosporine, procédés pour leur préparation et leur application
DE2720580A1 (de) Beta-lactam-verbindungen, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
DE3224866A1 (de) Ss-lactamantibiotika, verfahren zu deren herstellung sowie sie enthaltende mittel
DE2639429A1 (de) Chinoxalin-di-n-oxide, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
DE3229125A1 (de) 4h-1,4-benzothiazin-derivate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel, futterzusatzstoffe und konservierungsmittel
DE2658905A1 (de) Beta-lactam-antibiotica, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
EP0000891A1 (fr) Combinaisons synergétiques de pénicillines et compositions antibiotiques les contenant
DE2447626A1 (de) Verfahren zur herstellung von neuen penicillinen sowie ihre verwendung als arzneimittel

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed
AK Designated contracting states

Designated state(s): BE CH DE FR GB LU NL SE

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Designated state(s): BE CH DE FR GB LU NL SE

REF Corresponds to:

Ref document number: 2860275

Country of ref document: DE

Date of ref document: 19810205

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: LU

Payment date: 19810722

Year of fee payment: 4

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19810731

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 19810731

Year of fee payment: 4

Ref country code: SE

Payment date: 19810731

Year of fee payment: 4

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: BE

Payment date: 19810930

Year of fee payment: 4

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Effective date: 19820718

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Effective date: 19830117

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Effective date: 19830201

NLV4 Nl: lapsed or anulled due to non-payment of the annual fee
PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 19890617

Year of fee payment: 12

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CH

Payment date: 19890630

Year of fee payment: 12

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 19890717

Year of fee payment: 12

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 19890731

Year of fee payment: 12

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Effective date: 19900717

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CH

Effective date: 19900731

GBPC Gb: european patent ceased through non-payment of renewal fee
REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FR

Effective date: 19910329

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Effective date: 19910403

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST

EUG Se: european patent has lapsed

Ref document number: 78100407.2

Effective date: 19850611

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT