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EP0000393A1 - Composés bêta-lactames, procédé pour leur préparation et leur utilisation - Google Patents

Composés bêta-lactames, procédé pour leur préparation et leur utilisation Download PDF

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Publication number
EP0000393A1
EP0000393A1 EP78100356A EP78100356A EP0000393A1 EP 0000393 A1 EP0000393 A1 EP 0000393A1 EP 78100356 A EP78100356 A EP 78100356A EP 78100356 A EP78100356 A EP 78100356A EP 0000393 A1 EP0000393 A1 EP 0000393A1
Authority
EP
European Patent Office
Prior art keywords
compounds
formula
salts
group
bacteria
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.)
Withdrawn
Application number
EP78100356A
Other languages
German (de)
English (en)
Inventor
Michael Dr. Preiss
Hans-Bodo Dr. König
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
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 EP0000393A1 publication Critical patent/EP0000393A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/195—Antibiotics
    • 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 present invention relates to new ⁇ -lactam compounds, a process for their preparation and their use as medicaments, in particular as antibacterial agents and as agents for promoting the growth and improving the feed conversion in animals.
  • the compounds according to the invention have excellent tolerability.
  • alkyl in alkyl-CO-O preferably denotes alkyl having 1 to 4, in particular 1 or 2, carbon atoms. Examples include methyl and ethyl, with methyl being particularly preferred.
  • the heterocyclic ring Het in -S-Het (definition of T) consists of 5 or 6 ring members and contains 1 to 4, preferably 1 to 3 identical or different heteroatoms, with oxygen, sulfur and nitrogen as heteroatoms.
  • the heterocyclic ring is preferably unsaturated and particularly preferably contains 2 double bonds.
  • the heterocyclic ring can contain one or more, preferably 1 or 2, in particular one, substituent.
  • substituents are: halogen, such as fluorine, chlorine and bromine, preferably chlorine and bromine, amino, lower alkylamino, di-lower alkylamino, lower alkyl, cycloalkyl (with 3 to 7, preferably 5 or 6 carbon atoms in the cycloalkyl part), lower alkyloxy, trifluoromethyl, phenyl, benzyl and acylamino with preferably 2 to 5, in particular 2 or 3, carbon atoms.
  • halogen such as fluorine, chlorine and bromine, preferably chlorine and bromine
  • amino lower alkylamino, di-lower alkylamino, lower alkyl, cycloalkyl (with 3 to 7, preferably 5 or 6 carbon atoms in the cycloalkyl part), lower alkyloxy, trifluoromethyl, phenyl, benzyl and acylamino with preferably 2 to 5, in particular 2 or 3, carbon atoms.
  • -S-Het as particularly
  • the -S-phenyl radical in the definition of T can carry one or more, preferably 1 to 3, in particular 1 or 2 identical or different substituents, preference being given to those which are listed above as possible substituents for the -S-Het radical .
  • Halogen W represents fluorine, chlorine and bromine, preferably bromine or chlorine, in particular chlorine.
  • Nucleofugic leaving groups in the definition of W are to be understood as meaning all nucleofugic groups commonly used in organic chemistry and above all those which are described in Angewandte Chemie, 81 (1969), page 543.
  • Pharmaceutically usable salts of the compounds of the formula I are salts of these compounds with inorganic and organic bases on the acidic carboxyl group or the acidic carboxyl and sulfonic acid groups. All 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.
  • organic amines examples include: di- and tri-lower alkylamines, e.g. B. diethylamine, triethylamine, tri-ß-hydroxyethylamine, procain, dibenzylamine, N, N'-dibenzylethylenediamine, N-benzyl-ß-phenyl-ethylamine, N-methyl and N-ethylmorpholine, 1-ephenamine, dehydroabiet y l- amine, N, N'-bis-dehydroabietylethylenediamine, N-lower alkyl piperidine.
  • So-called basic amino acids such as lysine or arginine can also advantageously be used as bases.
  • Particularly preferred salts are the sodium salts.
  • Preferred salts of the compounds of the formula II are salts with bases which are listed as being suitable for salt formation with compounds of the formula I.
  • the sodium salts are particularly preferred.
  • the compounds of general formula III used as starting materials can be obtained by known methods. You can e.g. B. can be obtained in the following way (see also JACS 78 (1956) 5349):
  • Suitable diluents in the process according to the invention are water and all inert organic solvents, preferably those which are miscible with water.
  • These include especially lower dialkyl ketones, e.g. B. acetone, methyl ethyl ketone, cyclic ethers, for example tetrahydrofuran and dioxane; Nitriles, for example acetonitrile; lower dialkylformamides, for example dimethylformamide; lower alkyl alcohols, for example, ethanol and isopropanol and dimethyl sulfoxide.
  • These solvents can also be used in mixtures with one another and in any mixtures of one or more of these solvents with water.
  • the process according to the invention can therefore be carried out in the presence of: (a) exclusively water, (b) exclusively one or more organic solvents or (c) water and one or more organic solvents. If, due to the presence in front of water, a pH measurement is hesitant during the reaction according to the invention, the pH of the reaction mixture is preferably kept between 6.5 to 7.5 by adding bases or by using buffer mixtures.
  • the Ver But driving can also be carried out very well in a different pH range, for example between 4.5 and 9.0 or at pH 2.0 to 4.5. It is also possible to react in water-immiscible solvents, e.g. B.
  • halogenated hydrocarbons such as chloroform or methylene chloride
  • organic bases preferably lower alkylamines, for. B. triethylamine, diethylamine or cyclic bases, e.g. B. N-ethyl piperidine.
  • the reaction can be carried out in a mixture of water and a water-immiscible solvent, such as. B.
  • lower alkyl ethers such as diethyl ether, halogenated hydrocarbons such as chloroform and methylene chloride; Carbon disulfide; Isobutyl methyl ketone; Esters such as ethyl acetate; perform aromatic hydrocarbons such as benzene, it being advisable to stir vigorously and to adjust the pH by adding a base or using conventional buffer solutions, e.g. B. phosphate, acetate or citrate buffer, between 4.5 and 9, o or z. B. 2, 0 and 4.5 to keep.
  • the reaction can also be carried out in water alone in the absence of organic solvents in the presence of an organic or inorganic base or with the addition of customary buffer substances.
  • Acid binders customarily used in the chemistry of antibiotics can be used as acid binders. These include inorganic bases and organic bases, which, for. B. are difficult to acylate due to steric hindrance. Examples of inorganic bases include sodium and potassium hydroxide. Practically all open-chain or cyclic ones which are difficult or difficult to acylate come as organic bases Amines and also heteroaromatic bases in question. Examples of bases are tertiary amines, preferably lower alkylamines, e.g. B. Triethylamine and / or cyclic bases, e.g. B. Pyridine and dicyclohexylamine called secondary amine, which is difficult to acylate.
  • bases are tertiary amines, preferably lower alkylamines, e.g. B. Triethylamine and / or cyclic bases, e.g. B. Pyridine and dicyclohexylamine called secondary amine, which is difficult to
  • the addition of a base is only necessary if acidic compounds are formed during the reaction, e.g. in the case where W is halogen or azide s +.
  • reaction temperatures can be varied within a wide range. In general, between about -20 ° C and about + 50 ° C, preferably between 0 and +20 0 C. However, as with most chemical reactions, higher or lower temperatures can in principle also be used.
  • the reaction can be carried out under normal pressure, but also under reduced or elevated pressure. Generally one works at normal pressure.
  • the proportions of the reactants of the formulas II and III can be varied within wide limits without the result being adversely affected.
  • the starting materials can e.g. are reacted with one another in equimolecular amounts.
  • the excess of the reactants of the general formula II can be easily removed because of the good solubility in aqueous mineral acids when working up the reaction mixture.
  • the reactants of the general formula III are also advantageous to use with an excess of, for example, 0.1 to 1.0 molar equivalents.
  • the reactants of the general formula II are better utilized and the decomposition of the reactants of the general formula III taking place as a side reaction in water-containing solvents is compensated. Since the compounds of the general formula III added in excess quickly convert into neutral nitrogen-containing heterocycles in water which can be easily removed, the purity of the antibiotics is hardly impaired thereby.
  • the amount of bases that may be used is e.g. B, determined by the desired compliance with a certain pH value. Where there is no pH measurement and adjustment, or because of the lack of sufficient amounts of water in the diluent it is not possible or is not sensible, 2 molar equivalents of base are preferably added.
  • reaction batches for the preparation of the compounds according to the invention and their salts are worked up in the manner generally known for these bodies. Also the isolation and purification of the compounds according to the invention and the release of the free acids from salts or the conversion of the free acids into salts are carried out according to generally accepted methods of organic chemistry, which are familiar to any person skilled in the art.
  • the compounds of the general formula I are both crystalline and amorphous in the form of the free acid and are both antibacterially active in the same way both anhydrous and in various forms of hydrate.
  • the compounds of general formula I are also in the form of their salts, e.g. B. sodium salts, both crystalline and amorphous and both anhydrous and water-containing, for example as a hydrate, antibacterial in the same way.
  • the active compounds according to the invention have a strong and broad antimicrobial activity. 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 active compounds according to the invention are active against a very broad spectrum of microorganisms. With their help, gram-negative and gram-positive bacteria and bacteria-like microorganisms can be combated and the diseases caused by these pathogens can be prevented, improved and / or cured.
  • the active compounds 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.
  • Non-toxic, inert pharmaceutically suitable excipients are to be understood as solid, semisolid or liquid diluents, fillers and formulation auxiliaries of all kinds.
  • Tablets, dragees, capsules, pills, granules, suppositories, solutions, suspensions and emulsions, pastes, ointments, gels, creams, lotions, powders and sprays may be mentioned as preferred pharmaceutical preparations.
  • Tablets, coated tablets, 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, polyvinyl pyrrolidone, (c) humectants, e.g. Glycerin, (d) disintegrant, e.g. Agar, calcium carbonate and sodium carbonate, (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, polyvinyl pyrrolidone
  • humectants e
  • quaternary ammonium compounds (g) wetting agents, e.g. Cetyl alcohol, glycerol monostearate, (h) adsorbent e.g. Kaolin and eentonite 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. Cetyl alcohol, glycerol monostearate
  • adsorbent e.g. Kaolin and eentonite
  • 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 customary coatings and casings optionally containing opacifying agents and can also be composed in such a way that they release the active ingredient (s) only or preferably in a certain part of the intestinal tract, possibly with a delay, with embedding materials e.g. Polymer substances and waxes can be used.
  • the active ingredient (s) can, if appropriate, also be present in microencapsulated form with one or more of the carrier substances specified above.
  • suppositories can contain the usual water-soluble or water-insoluble excipients, for example polyethylene glycols, fats, for example cocoa fat and higher esters (for example C 14 alcohol with C 16 fatty acid) or mixtures of these substances.
  • water-soluble or water-insoluble excipients for example polyethylene glycols, fats, for example cocoa fat and higher esters (for example C 14 alcohol with C 16 fatty acid) or mixtures of these substances.
  • ointments, pastes, creams and gels can contain the usual carriers, e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc and zinc oxide or mixtures of these substances.
  • carriers e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc and zinc oxide or mixtures of these substances.
  • Powders and sprays can contain the usual excipients in addition to the active ingredient (s), 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. Contain chlorofluorocarbons.
  • solutions and emulsions can include the usual carrier substances such as solvents, solubilizers and emulsifiers, for example water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3 - butylene glycol, dimethylformamide, oils, in particular cottonseedol, Contain peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerin, glycerin formal, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan or mixtures of these substances.
  • solvents such as solvents, solubilizers and emulsifiers, for example water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene
  • solutions and emulsions can also be in sterile and blood isotonic form.
  • suspensions can contain the usual carriers such as liquid diluents, e.g. Contain water, ethyl alcohol, propylene glycol, suspending agents, e.g., ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth or mixtures of these substances.
  • liquid diluents e.g. Contain water, ethyl alcohol, propylene glycol
  • suspending agents e.g., ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth or mixtures of these substances.
  • the formulation forms mentioned can also contain colorants, preservatives and additives which improve the smell and taste, e.g. Peppermint oil and eucalyptus oil and sweeteners, e.g. Saccharin.
  • the therapeutically active compounds 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 further pharmaceutical active substances.
  • 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.
  • the present invention also includes the use of the active compounds according to the invention and of pharmaceutical preparations which contain one or more active compounds according to the invention in human and veterinary medicine for preventing, ameliorating and / or curing the diseases mentioned above.
  • the active compounds or the pharmaceutical preparations can be administered locally, orally, parenterally, intraperitoneally and / or rectally, preferably orally or parenterally, such as intravenously or intramuscularly.
  • the active ingredient (s) 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, optionally in the form of several individual doses to deliver the results you want.
  • a single dose contains the active ingredient (s) according to the invention, preferably in amounts of about 1 to about 250, in particular 10 to 100 mg / kg of body weight.
  • the new compounds When used as a feed additive, the new compounds can be given in the usual concentrations and preparations 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 cephalosporins are characterized by strong antibacterial effects, which have been tested in vivo and in vitro, and by oral resorbability.
  • cephalosporins according to the invention can be used with other antimicrobial agents, e.g. can be combined with penicillins that are particularly resistant to penicillinase. Such a combination would be e.g. those with oxacillin or dicloxacillin.
  • cephalosporins according to the invention can also be combined with aminoglycoside antibiotics, such as, for example, gentamicin, kanamicin, amikacin or tobramycin, for the purpose of widening the spectrum of activity and to achieve an increase in activity.
  • aminoglycoside antibiotics such as, for example, gentamicin, kanamicin, amikacin or tobramycin
  • the ED 100 is the dose at which 100% of the infected animals survive after 24 hours.
  • aqueous solution is extracted once with ethyl acetate, cooled to 5 °, covered with 1CO vol.
  • the acid is suspended in 50 parts by volume of water (5 °) and 0.3N sodium hydroxide solution is added dropwise in such a way that a pH range between 6.0 and 7.5 can be maintained. After the acid has almost completely dissolved (final pH 7.5), the mixture is filtered and the light brown solution is freeze-dried. 5.0 parts by weight are obtained. (59.3%) with a decomp. of 235 °.
  • the ß-lactam content is 95% (HPLC).

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Food Science & Technology (AREA)
  • Zoology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Animal Husbandry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cephalosporin Compounds (AREA)
EP78100356A 1977-07-16 1978-07-11 Composés bêta-lactames, procédé pour leur préparation et leur utilisation Withdrawn EP0000393A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE2732323 1977-07-16
DE19772732323 DE2732323A1 (de) 1977-07-16 1977-07-16 Beta-lactam-verbindungen, verfahren zu ihrer herstellung sowie ihre verwendung

Publications (1)

Publication Number Publication Date
EP0000393A1 true EP0000393A1 (fr) 1979-01-24

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Application Number Title Priority Date Filing Date
EP78100356A Withdrawn EP0000393A1 (fr) 1977-07-16 1978-07-11 Composés bêta-lactames, procédé pour leur préparation et leur utilisation

Country Status (8)

Country Link
EP (1) EP0000393A1 (fr)
JP (1) JPS5419992A (fr)
AU (1) AU3796078A (fr)
DE (1) DE2732323A1 (fr)
DK (1) DK318378A (fr)
ES (1) ES471771A1 (fr)
IL (1) IL55131A0 (fr)
IT (1) IT7825712A0 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0176716A1 (fr) * 1984-08-25 1986-04-09 Bayer Ag Sels de sodium cristallin de l'acide D-6-(alpha-[(2-oxo-3-furfuryliden-amino-imidazolidin-1-yl)carbonylamin]-thiényl-2-acétamido)-pénicillanique, procédé de préparation et application dans des médicaments

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5850799A (ja) * 1981-09-21 1983-03-25 株式会社栄工業所 パネル電気メッキ方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2456307A1 (de) * 1974-11-28 1976-08-12 Bayer Ag Beta-lactam-antibiotica, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
DE2512998A1 (de) * 1975-03-25 1976-10-07 Bayer Ag Beta-lactam-antibiotica, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
DE2525541A1 (de) * 1975-06-07 1976-12-16 Bayer Ag Beta-lactam-antibiotica, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
FR2359145A1 (fr) * 1976-07-23 1978-02-17 Bayer Ag Nouveaux antibiotiques du type b-lactame, leur procede de preparation et medicament les contenant
DE2658718A1 (de) * 1976-12-24 1978-06-29 Bayer Ag Methoxy-beta-lactam-antibiotica, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2456307A1 (de) * 1974-11-28 1976-08-12 Bayer Ag Beta-lactam-antibiotica, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
DE2512998A1 (de) * 1975-03-25 1976-10-07 Bayer Ag Beta-lactam-antibiotica, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
DE2525541A1 (de) * 1975-06-07 1976-12-16 Bayer Ag Beta-lactam-antibiotica, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
FR2359145A1 (fr) * 1976-07-23 1978-02-17 Bayer Ag Nouveaux antibiotiques du type b-lactame, leur procede de preparation et medicament les contenant
DE2658718A1 (de) * 1976-12-24 1978-06-29 Bayer Ag Methoxy-beta-lactam-antibiotica, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0176716A1 (fr) * 1984-08-25 1986-04-09 Bayer Ag Sels de sodium cristallin de l'acide D-6-(alpha-[(2-oxo-3-furfuryliden-amino-imidazolidin-1-yl)carbonylamin]-thiényl-2-acétamido)-pénicillanique, procédé de préparation et application dans des médicaments

Also Published As

Publication number Publication date
IL55131A0 (en) 1978-09-29
AU3796078A (en) 1980-01-17
DK318378A (da) 1979-01-17
ES471771A1 (es) 1979-02-01
JPS5419992A (en) 1979-02-15
DE2732323A1 (de) 1979-01-25
IT7825712A0 (it) 1978-07-14

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