EP0000891B1 - Combinaisons synergétiques de pénicillines et compositions antibiotiques les contenant - Google Patents

Combinaisons synergétiques de pénicillines et compositions antibiotiques les contenant Download PDF

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Publication number
EP0000891B1
EP0000891B1 EP78100603A EP78100603A EP0000891B1 EP 0000891 B1 EP0000891 B1 EP 0000891B1 EP 78100603 A EP78100603 A EP 78100603A EP 78100603 A EP78100603 A EP 78100603A EP 0000891 B1 EP0000891 B1 EP 0000891B1
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EP
European Patent Office
Prior art keywords
methyl
active compound
penicillin
compound combination
combination according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
EP78100603A
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German (de)
English (en)
Other versions
EP0000891A1 (fr
Inventor
Karl Georg Dr. Metzger
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
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Bayer AG
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Publication date
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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
    • 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 new antibiotic synergistic combinations of active ingredients from known penicillins.
  • the drug combinations consist of two groups of drugs.
  • the active compounds of the first group (group A) are the known penicillins Da - [(imidazolidin-2-one-1-yl) carbonylamino] benzylpenicillin (US Pat. No. 3,933,795) and Da - [(3-methylsulfonylimidazolidin-2 -on-1-yl) -carbonylamino] -benzylpenicillin (German Offenlegungsschrift 2152967).
  • the active substances of the second group (group B) are the known penicillins 3- (2,6-dichlorophenyl) -5-methyl-4-isoxazolylpenicillin, 3- (2-chloro-6-fluorophenyl) -5-methyl-4-isoxazolylpenicillin , 3- (2-chlorophenyl) -5-methyl-4-isoxazolylpenicillin, 3-phenyl-5-methyl-4-isoxazolylpenicillin and 2,6-dimethoxyphenylpenicillin.
  • synergistic active ingredient combinations according to the invention are characterized in that they contain at least one penicillin from active ingredient group A and at least one penicillin from active ingredient group B.
  • the active ingredients can be present in the acid or salt form and in the possible crystal and hydrate forms.
  • the molar ratio of the active ingredients in group A to those in group B can be in the range from 9: 1 to 1: 9. It is preferably in the range from 3: 1 to 1: 3 and very particularly preferably 1: 1.
  • the penicillin D- ⁇ - [(3-methylsulfonyl-imidazolidin-2-one-1-yl) -carb-onylamino] -benzylpenicillin is preferred.
  • penicillin 3-phenyl-5-methyl-4-isoxazolylpenicillin is preferred.
  • active substances of group A or B are present as salts, these are pharmaceutically usable salts of the acidic carboxyl group of these active substances with inorganic or organic bases.
  • bases normally used in pharmaceutical chemistry in particular in the chemistry of antibiotics, can be used as bases for this purpose.
  • inorganic bases are: alkali and alkaline earth metal hydroxides, alkali and alkaline earth metal carbonates and alkali metal hydrogen carbonates, such as sodium and potassium hydroxide, calcium and magnesium hydroxide, sodium and potassium carbonate, calcium carbonate, sodium and potassium hydrogen carbonate; Aluminum hydroxide and ammonium hydroxide.
  • Primary, secondary and tertiary aliphatic amines and heterocyclic amines can be used as organic amines.
  • examples include his: di- and tri-lower alkylamines, e.g. Diethylamine, triethylamine, tri- ⁇ -hydroxyethylamine, procain, dibenzylamine, N, N'-di-benzylethylenediamine, N-benzyl- ⁇ -phenyl-ethylamine, N-methyl- and N-ethylmorpholine, I-ephenamine, dehydroabietylamine, N, N'-bis-dehydro-abietyl-ethylenediamine, N-lower alkyl piperidine.
  • di- and tri-lower alkylamines e.g. Diethylamine, triethylamine, tri- ⁇ -hydroxyethylamine, procain, dibenzylamine, N, N'-di-benzylethylenediamine
  • So-called basic amino acids such as lysine or arginine can also advantageously be used as bases.
  • Particularly preferred salts are the sodium salts.
  • the synergistic active substance mixtures according to the invention have a strong and broad antimicrobial activity with low toxicity. These properties enable their use as chemotherapeutic agents in medicine and as substances for the preservation of inorganic and organic materials, in particular of all kinds of organic materials, e.g. Polymers, lubricants, paints, fibers, leather, paper and wood, food and water.
  • organic materials e.g. Polymers, lubricants, paints, fibers, leather, paper and wood, food and water.
  • the synergistic active ingredient mixtures according to the invention are active against a very broad spectrum of microorganisms. With their help, gram-negative and gram-positive bacteria and bacterial-like microorganisms can be combated for the first time without problems and the diseases caused by these pathogens can be prevented, improved and / or cured.
  • the synergistic 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.
  • local and / or systemic diseases that are caused by the following pathogens or by a mixture of the following pathogens can be treated and / or prevented:
  • Enterobacteriaceae such as Escherichiae bacteria from the Coli group: Escherichia bacteria, e.g. Escherichia coli, Klebsiella bacteria, e.g. K.pneumoniae, K.pneumoniae, Proteae bacteria of the Proteus group: Proteus, e.g. Proteus vulgaris, Pr.morganii, Pr.rettgeri.
  • diseases which can be prevented, improved and / or cured by the synergistic active substance mixtures according to the invention are: diseases of the respiratory tract and throat; Otitis; Pharyngitis; Pneumonia; Peritonitis; Pyelonephritis; Cystitis; Endocarditis; System infections; Bronchitis; Arthritis; local infections.
  • the present invention includes pharmaceutical preparations which, in addition to inert pharmaceutically suitable carriers and / or additives, contain an active ingredient combination according to the invention or which consist of an active ingredient combination according to the invention.
  • the therapeutically active synergistic active ingredient mixtures should preferably be present in the pharmaceutical preparations listed above in a total 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 substance or substances with the carrier substance or substances.
  • synergistic active substance mixtures or their pharmaceutical preparations can be administered locally, orally, parenterally, intraperitoneally and / or rectally, preferably orally or parenterally, such as intravenously or intramuscularly.
  • the active compounds according to the invention in total amounts of about 5 to about 1000, preferably 20 to 200 mg / kg of body weight per 24 hours, if appropriate in the form of a number of individual doses to deliver the desired results.
  • a single dose contains the active ingredient mixture according to the invention, preferably in amounts of about 1 to about 250, in particular 10 to 100 mg / kg of body weight.
  • an ampoule contains, for example, 2 g of Da - [(3-methylsulfonyl-imidazolidin-2-one-1-yi) -carbonylamino] -benzylpenicillin and 1 g of 3-phenyl-5-methyl-4-isoxazolylpenicillin .
  • the new synergistic active substance mixtures in the usual concentrations and preparations can be given together with the feed or with feed preparations or with the drinking water. This can prevent, ameliorate and / or cure an infection by gram-negative or gram-positive bacteria and also promote growth and improve the utilization of the feed.
  • the new synergistic active ingredient mixtures are characterized by strong antibacterial effects, which have been tested in vivo and in vitro, and by oral resorbability.

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  • 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)

Claims (9)

1. Mélange de substances actives à effet combiné, caractérisé en ce qu'il renferme:
(A) au moins une pénicilline choisie dans le groupe comprenant la D-a-[(imidazolidine-2-one-1-yl)-carb- onylamino]-benzylpénicilline, la D-a-[(3-méthylsulf- onylimidazolidine-2-one-1 -yl)-carbonylamino]-benzyl- pénicilline et/ou leurs sels acceptables du point de vue pharmaceutique et
(B) au moins une pénicilline choisie dans le groupe comprenant la 3-(2,6-dichlorphényl)-5-méthyl-4-isoxazolylpénicilline, la 3-(2-chloro-6-fluorophényl)-5-méthyl-4-isoxazolylpénicilline, la 3-(2-chlorophényl)-5-méthyl-4-isoxazolylpénicilline, la 3-phényl-5-mé- thyl-4-isoxazolylpénicilline, la 2,6-diméthoxyphényl- pénicilline et/ou leurs sels acceptables du point de vue pharmaceutique.
2. Mélange de substances actives suivant la revendication 1, caractérisé en ce qu'il est formé de D-a-[(3-méthylsulfonylimidazolidine-2-one-1-yl)-carbonylami- no]-benzylpénicilline et de 3-phényl-5-méthyl-4-isoxa- zolylpénicilline.
3. Mélange de substances actives suivant la revendication 1, caractérisé en ce qu'il est formé de D-a-[(3-méthylsulfonylimidazolidine-2-one-1-yl)-carbonylami- no]-benzylpénicilline et de 3-(2,6-dichlorophényl)-5-méthyl-4-isoxazolylpénicilline.
4. Mélange de substances actives suivant la revendication 1, caractérisé en ce qu'il est formé de D-a-[(imidazolidine-2-one-1 -yl)-carbonylamino]-benzylpé- nicilline et de 3-phényl-5-méthyl-4-isoxazolylpénicil- line.
5. Mélange de substances actives suivant la revendication 1, caractérisé en ce qu'il est formé de D-a-[(imidazolidine-2-one-1-yl)-carbonylamino]-benzylpé- nicilline et de 3-(2,6-dichlorophényl)-5-méthyl-4-isoxazolylpénicilline.
6. Mélange de substances actives suivant l'une quelconque des revendications 1 à 5, caractérisé en ce que les substances actives sont présentes sous la forme des sels de sodium.
7. Mélange de substances actives suivant l'une quelconque des revendications 1 à 6, caractérisé en ce que le rapport en poids du composant (A) au composant (B) est compris dans la plage de 9 : 1 à 1 : 9 et de préférence dans la plage de 3 : 1 à 1 : 3.
8. Mélange de substances actives suivant la revendication 7, caractérisé en ce que le rapport en poids du composant (A) au composant (B) est égal à 1 : 1.
9. Composition antibiotique, caractérisée en ce qu'elle contient un mélange de substances actives à effet combiné suivant la revendication 1.
EP78100603A 1977-08-20 1978-08-07 Combinaisons synergétiques de pénicillines et compositions antibiotiques les contenant Expired EP0000891B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE2737673 1977-08-20
DE19772737673 DE2737673A1 (de) 1977-08-20 1977-08-20 Synergistische kombinationen von penicillinen

Publications (2)

Publication Number Publication Date
EP0000891A1 EP0000891A1 (fr) 1979-03-07
EP0000891B1 true EP0000891B1 (fr) 1980-01-09

Family

ID=6016945

Family Applications (1)

Application Number Title Priority Date Filing Date
EP78100603A Expired EP0000891B1 (fr) 1977-08-20 1978-08-07 Combinaisons synergétiques de pénicillines et compositions antibiotiques les contenant

Country Status (6)

Country Link
US (1) US4529591A (fr)
EP (1) EP0000891B1 (fr)
JP (1) JPS5444033A (fr)
AT (1) AT362871B (fr)
DE (2) DE2737673A1 (fr)
IT (1) IT1098187B (fr)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1175590A (en) * 1967-08-09 1969-12-23 Beecham Group Ltd Therapeutic Compositions
BE756856A (fr) * 1969-09-30 1971-03-01 Chinoin Gyogyszer Es Vegyeszet Compositions antibiotiques nouvelles possedant un effet therapeutique accru et leur preparation
GB1471235A (en) * 1974-09-18 1977-04-21 Beecham Group Ltd Amoxycillin derivatives

Also Published As

Publication number Publication date
IT7826847A0 (it) 1978-08-18
AT362871B (de) 1981-06-25
DE2737673A1 (de) 1979-02-22
EP0000891A1 (fr) 1979-03-07
ATA602278A (de) 1980-11-15
US4529591A (en) 1985-07-16
DE2857518D1 (en) 1980-02-14
JPS5444033A (en) 1979-04-07
IT1098187B (it) 1985-09-07

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