COMPOSITION CONTAINING A PENEM OR CARBAPENEM ANTIBIOTIC

Abstract: Administration of an N -acylated amino acid in association with a penem or carbapenem antibiotic relieves or eliminates the renal problems associated with administration of the antibiotic alone. The amino acid derivative and antibiotic may be formulated together as a composition or administered separately, either simultaneously or sequentially. The composition may be prepared by simple mixing.

Description: The present invention relates to a novel composition comprising a penem or carbapenem antibiotic in association with an amino acid derivative. The class of compounds known as "penem and carbapenem antibiotics" is, of course, very well known and is potentially of great value for the treatment of bacterial infections. Although, as a group, these penem and carbapenem antibiotics exhibit excellent anti-bacterial activity and a variety of other properties which render them highly suitable for pharmaceutical use, they do have a number of disadvantages. One of the problems of these antibiotics is that, in general, they exhibit a degree of renal toxicity, and some degree of kidney damage is a frequent side effect of their use; accordingly, such penem and carbapenem antibiotics should not be used for the treatment of patients with actual or suspected impaired renal function. As a result, the penem and carbapenem antibiotics cannot be used for many patients for whom otherwise they would be the antibiotic of choice. The problem of renal toxicity is particularly acute when the antibiotics are administered by intravenous or intramuscular injection in a high dose. We have now surprisingly discovered that the concurrent, or effectively concurrent, administration, with the penem or carbapenem antibiotic, of one or more of a certain class of acylated amino acid derivatives significantly reduces this renal toxicity. EP-A-0 00 7614 discloses the use of a dipeptidase inhibitor in associated with antibiotics similar to those to which the present invention relates. However, the dipeptidase inhibitors employed are structurally different from the amino acid derivatives of the present invention and are employed for a totally different purpose. The amino acid derivatives employed in the present invention possess little or no dipeptidase inhibitory activity. Accordingly, in one aspect, the present invention provides a composition comprising: (a) a penem or carbapenem antibiotic; and (b) a pharmaceutically acceptable N -acylated derivative of an amino acid wherein the amino group and the carboxylic acid group are attached to a saturated aliphatic carbon chain or carbon atom, or a salt thereof, provided that, where the composition comprises only one amino acid derivative, the amino acid is not ornithine, lysine, phenylalanine or phenylglycine. EP-A-0 178 911 discloses such a composition where the amino acid is ornithine, lysine, phenylalanine or phenylglycine. There is no particular limitation on the nature of the penem or carbapenem antibiotic to which the present invention can be applied and it is believed that the beneficial effects of the concurrent administration of the N -acylated amino acid derivative will be achieved regardless of the particular antibiotic chosen. However, the penem and carbapenem antibiotics which are currently of most actual or potential interest may be represented by the general formula I: in which: Y represents a sulphur atom, a methylene group or a methylene group having 1 or 2 methyl and/or methoxy substituents; and R¹ represents a C₁-C₆ alkyl group, a C₁-C₆ alkyl group having at least one of substituents (i) or a heterocyclic group having from 4 to 14 ring atoms of which from 1 to 5 are nitrogen and/or oxygen and/or sulphur hetero-atoms where said heterocyclic group is unsubstituted or has at least one of substituents (ii); substituents (i): halogen atoms, amino groups, amino groups having at least one of substituents (iii), C₁-C₄ alkylideneamino groups, C₁-C₄ aminoalkylideneamino groups, amidino groups, amidino groups having from 1 to 3 of substituents (iii), heterocyclic groups having from 4 to 14 ring atoms of which from 1 to 5 are nitrogen and/or oxygen and/or sulphur hetero-atoms wherein said heterocyclic group is unsubstituted or has at least one of substituents (ii), imino groups, cyano groups, carbamoyl groups and carbamoyl groups having at least one C₁-C₄ alkyl and/or C₁-C₄ alkoxy substituent; substituents (ii): C₁-C₆ alkanimidoyl groups, C₁-C₆ alkyl groups, alkoxyalkyl groups where the alkoxy and alkyl parts are each C₁-C₄, carbamoyl groups, carbamoyl groups having at least one C₁-C₄ alkyl and/or C₁-C₄ alkoxy substituent, C₁-C₄ haloalkyl groups, heterocyclic acylimidoyl groups where the heterocyclic part has from 5 to 9 ring atoms of which from 1 to 3 are nitrogen and/or oxygen and/or sulphur hetero-atoms, amidino groups, amidino groups having from 1 to 3 of substituents (iii), imino groups, oxygen atoms, C₁-C₆ alkanoyl groups, C₁-C₆ alkanesulphonyl groups, C₁-C₆ alkanesulphinyl groups, hydroximino groups, C₁-C₄ alkoximino groups, carbamoyloxy groups, carbamoyloxy groups having at least one C₁-C₄ alkyl and/or C₁-C₄ alkoxy substituent, carbamoyloxyalkyl groups where the alkyl part is C₁-C₄ and the carbamoyl part is unsubstituted or has at least one C₁-C₄ alkyl and/or C₁-C₄ alkoxy substituent and C₁-C₄ iminoalkyl groups; substituents (iii): C₁-C₆ alkyl groups, C₂-C₆ alkenyl groups, C₂-C₆ alkynyl groups, and said alkyl, alkenyl and alkynyl groups having at least one substituent selected from halogen atoms, carbamoyloxy groups and carbamoyloxy groups having at least one C₁-C₄ alkyl and/or C₁-C₄ alkoxy substituent. Preferably Y represents a sulphur atom, a methylene group, or the group CH₃-CH<, CH₃O-CH< or (CH₃)₂C<. Preferred examples of groups which may be represented by R¹ include the ethyl, 2-fluoroethyl, 2-(aminomethyleneamino(ethyl, N ¹, N ¹-dimethylamidinomethyl, N ¹, N ¹, N ²-trimethylamidinomethyl, 3-pyrrolidinyl, 1-formimidoyl-3-pyrrolidinyl, 1-acetimidoyl-3-pyrrolidinyl, 1-propionimidoyl-3-pyrrolidinyl, 2-methyl-1,4,5,6-tetrahydro-5-pyrimidinyl, 2-methoxymethyl-1,4,5,6-tetrahydro-5-pyrimidinyl, 3-azetidinyl, 1-acetimidoyl-3-azetidinyl, N ¹-methyl- N ¹-(2-propynyl)amidinomethyl, N ¹-(2-fluoroethyl)- N ¹-methylamidinomethyl, N ¹-(3-fluoropropyl)- N ¹-methylamidinomethyl, N ¹-methyl- N ¹-(2,2,2-trifluoroethyl)amidinomethyl, 1-(3-azetidinyl)ethyl, 1-(1-acetimidoyl-3-azetidinyl)ethyl, 1,4,5,6-tetrahydro-2-pyrimidinylmethyl, 1-(4,5-dihydro-2-thiazolyl)ethyl, 5-carbamoyl-3-pyrrolidinyl, 1-acetimidoyl-5-carbamoyl-3-pyrrolidinyl, 2-chloromethyl-1,4,5,6-tetrahydro-5-pyrimidinyl, 1-butyrimidoyl-3-pyrrolidinyl, 1-nicotinimidoyl-3-pyrrolidinyl, N ¹, N ¹-diallylamidinomethyl, N ¹-methyl- N ¹-(2-propynyl)amidino, N ¹-(2-fluoroethyl)- N ¹-methylamidino, N ¹-(3-fluoropropyl)- N ¹-methylamidino, N ¹-methyl- N ¹-(2,2,2-trifluoroethyl)amidino, N ¹-allyl- N ¹-methylamidinomethyl, cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 2-cyano-1-methylethyl, 2-aminoethyl, 1-carbamoylethyl, 2-(1-aminoethylideneamino)ethyl, 1-amidino-3-pyrrolidinyl, 2-methyl-1,3-diazabicyclo[3.3.0]oct-2-en-7-yl, 2-methoxymethyl-1,3-diazabicyclo[3.3.0]oct-2-en-7-yl, 5-imino-2-pyrrolidinyl, 2-imino-5-piperidinyl, 1-acetimidoyl-5-methylcarbamoyl-3-pyrrolidinyl, 1-acetimidoyl-5-methoxycarbamoyl-3-pyrrolidinyl, 2-imino-2-( S -oxothiomorpholino)ethyl, 2-imino-2-(1,1-dioxo-1,3-thiazolidin-3-yl)ethyl, 2-imino-2-( S , S -dioxothiomorpholino)ethyl, 2-imino-2-(3,5-dioxo-1-piperazinyl)ethyl, 2-imino-2-(4-methyl-3,5-dioxo-1-piperazinyl)ethyl, 2-imino-2-(3-oxo-1-piperazinyl)ethyl, 2-imino-2-(4-methyl-3-oxo-1-piperazinyl)ethyl, 2-imino-2-(4-acetyl-3-oxo-1-piperazinyl)ethyl, 2-imino-2-(4-methanesulphonyl-3-oxo-1-piperazinyl)ethyl, N ¹-(2-carbamoyloxyethyl)- N ¹-methylamidinomethyl, 2-(3-hydroximino-1-pyrrolidinyl)-2-iminoethyl, 2-imino-2-(3-methoximino-1-pyrrolidinyl)ethyl, 2-(4-hydroximinopiperidino)-2-iminoethyl, 2-imino-2-(4-methoximinopiperidino)ethyl, 2-(3-carbamoyloxy-1-pyrrolidinyl)-2-iminoethyl, 2-imino-2-(3-oxo-1-piperazinyl)ethyl, 2-(3-carbamoylpiperidino)-2-iminoethyl, 2-(3-carbamoyloxypiperidino)-2-iminoethyl, 2-(2-carbamoyloxy-1-pyrrolidinyl)-2-iminoethyl, 2-(2-carbamoyloxymethyl-1-pyrrolidinyl)-2-iminoethyl, 2-(4-carbamoyloxypiperidino)-2-iminoethyl, 2-(4-formyl-1-piperazinyl)-2-iminoethyl, 2-(4-acetyl-1-piperazinyl)-2-iminoethyl, 1-formyl-3-azetidinyl, 1-iminomethyl-3-azetidinyl, 1-methyl-4-piperidyl, 1-acetimidoyl-4-piperidyl and 1-acetyl-3-pyrrolidinyl groups. The invention may also be applied to pharmaceutically acceptable salts and esters of such antibiotics, such as are well known in the art. Specific examples of compounds of general formula I which may be employed in the present invention are those in which R¹ and Y are as defined below: Of the compounds listed above, we particularly prefer those which have the same configuration as thienamycin, i.e. (5 R ,6 S )-6-[1( R )-hydroxyethyl]. In particular, the following compounds are preferred: (5 R ,6 S )-2-{2-[(aminomethylene)amino]ethylthio}-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (isomer of Compound No. 1) (5 R ,6 S )-2-[(3 S )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (isomer of Compound No. 6) (5 R ,6 S )-2-[(3 R )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (isomer of Compound No. 7) (5 R ,6 S )-2-[(3 R )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-1( S )-methyl-2-carbapenem-3-carboxylic acid (isomer of Compound No. 23) (5 R ,6 S )-2-[(3 S )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-1( R )-methyl-2-carbapenem-3-carboxylic acid (isomer of Compound No. 24) (5 R ,6 S )-2-[(3 S )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-1( S )-methyl-2-carbapenem-3-carboxylic acid (isomer of Compound No. 27) (5 R ,6 S )-2-[(3 S )-1-acetimidoyl-5( S )-carbamoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (isomer of Compound No. 28) The above compounds may likewise be employed in the form of their pharmaceutically acceptable salts or esters, examples of which are well-known to those skilled in the art and which are given, for example, in US Patent No. 4,552,873. The protective effect against renal toxicity appears to be exhibited by the whole range of amino acids wherein the amino and carboxylic acid groups are attached to a saturated aliphatic carbon chain or carbon atom. However, we have found that best results are achieved when employing N -acylated derivatives of those amino acids which may be represented by the general formula II: H₂N-X-COOH (II) wherein X represents a C₁-C₁₀ alkylene group or a C₁-C₁₀ alkylene group having at least one substituent selected from hydroxy groups, C₁-C₄ alkoxy groups, C₆-C₁₄ aryloxy groups, substituted C₆-C₁₄ aryloxy groups, C₇-C₉ aralkyloxy groups, substituted C₇-C₉ aralkyloxy groups, mercapto groups, C₁-C₄ alkylthio groups, C₆-C₁₄ arylthio groups, substituted C₆-C₁₄ arylthio groups, C₇-C₉ aralkylthio groups, substituted C₇-C₉ aralkylthio groups, C₂-C₅ carboxyalkylthio groups, amino groups, amino groups having one or two substituents selected from C₁-C₄ alkyl groups, C₆-C₁₄ aryl groups, substituted C₆-C₁₄ aryl groups, C₇-C₉ aralkyl groups, substituted C₇-C₉ aralkyl groups and carboxylic acyl groups, C₆-C₁₄ aryl groups, substituted C₆-C₁₄ aryl groups, carboxy groups, amidino groups, sulpho groups, C₁-C₄ alkylsulphinyl groups, C₁-C₄ alkylsulphonyl groups and heterocyclic groups having from 5 to 14 ring atoms of which from 1 to 5 are nitrogen and/or oxygen and/or sulphur hetero-atoms, said substituted aryloxy, aralkyloxy, arylthio, aralkylthio, aryl and aralkyl groups having at least one substituent selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups. In general terms, the N -acylated derivatives of these amino acids may be represented by the general formula III: R²HN-X-COOH (III) wherein R² represents a carboxylic acyl group and X is as defined above. Examples of carboxylic acyl groups which may be represented by R² include: alkanoyl groups, and preferably alkanoyl groups having from 1 to 18, more preferably from 1 to 10 and still more preferably from 1 to 8, e.g. from 2 to 5 or from 5 to 8, carbon atoms, for example the acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, heptanoyl, octanoyl, nonanoyl and decanoyl groups; in the case of those amino acids which have relatively bulky and lipophilic groups, lower (e.g. C₂-C₅) alkanoyl groups are preferred; for others (e.g. glycine), higher (e.g. C₅-C₈) groups are preferred; alkenoyl and alkynoyl groups, and more preferably such groups having from 3 to 8, more preferably 3 or 4, carbon atoms, for example the acryloyl, methacryloyl, crotonoyl or propioloyl groups; aromatic acyl groups in which the aryl ring is a carbocyclic ring having from 6 to 14, preferably 6 to 10, carbon atoms and optionally having from 1 to 5, more preferably from 1 to 3, substituents preferably selected from C₁-C₄ alkyl groups, hydroxy groups, C₁-C₄ alkoxy groups, amino groups, sulpho groups and halogen atoms, for example the benzoyl and naphthoyl (1- or 2-naphthoyl) groups and the benzoyl and naphthoyl (1- or 2-naphthoyl) groups having one or more of the above substituents, for example the p -toluoyl, m -toluoyl, o -toluoyl, 4-butylbenzoyl, 4-hydroxybenzoyl, 3-hydroxybenzoyl, 2-hydroxybenzoyl, 4-methoxybenzoyl, 3-methoxybenzoyl, 2-methoxybenzoyl, 4-butoxybenzoyl, 4-aminobenzoyl, 3-aminobenzoyl, 2-aminobenzoyl, 3-sulphobenzoyl, 4-chlorobenzoyl, 3-fluorobenzoyl, 2-bromobenzoyl, 3-hydroxy-2-naphthoyl and 1-hydroxy-2-naphthoyl groups; alicyclic acyl groups in which the carbocyclic ring has from 3 to 8 carbon atoms, more preferably from 3 to 6 carbon atoms, and in which the cycloalkane ring is unsubstituted or has at least one C₁-C₄ alkyl and/or phenyl substituent, for example the cyclopropanecarbonyl, cyclobutanecarbonyl, cyclopentanecarbonyl, cyclohexanecarbonyl, 1-phenyl-1-cyclopropanecarbonyl, 1-phenyl-1-cyclopentanecarbonyl, 1-methyl-1-cyclohexanecarbonyl and 1-phenyl-1-cyclohexanecarbonyl groups; araliphatic acyl groups in which the aryl ring is a carbocyclic ring having from 6 to 14, preferably 6 to 10, carbon atoms and optionally having from 1 to 5, more preferably from 1 to 3, substituents preferably selected from C₁-C₄ alkyl groups, hydroxy groups, C₁-C₄ alkoxy groups, amino groups, sulpho groups and halogen atoms, and in which the alkyl moiety has from 1 to 4 carbon atoms, such as the phenylacetyl, α-phenyl-α-methylacetyl, α-phenyl-α-ethylacetyl, α,α-diphenylacetyl, α-phenyl-α-cyclopentyl-acetyl, 3-phenylpropionyl, 4-phenylbutyryl, 4-tolylacetyl, 4-hydroxyphenylacetyl, 4-aminophenylacetyl, 4-methoxyphenylacetyl, 3-sulphophenylacetyl and 4-chlorophenylacetyl groups; heterocyclic acyl groups which may have saturated or unsaturated ring systems, the rings having 5 or 6 ring atoms, of which from 1 to 3 are nitrogen and/or sulphur and/or oxygen hetero-atoms and the ring being unsubstituted or having from 1 to 3 C₁-C₄ alkyl and/or hydroxy substituents, for example the nicotinoyl, 2-thiophenecarbonyl, 2-furoyl, 2-pyrazinecarbonyl, 2-piperidinecarbonyl, N -methylnicotinoyl and 6-hydroxynicotinoyl groups; alkoxycarbonyl groups having a total of from 2 to 7 carbon atoms, for example the methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, t-butoxycarbonyl and pentyloxycarbonyl groups; and aralkyloxycarbonyl groups in which the aralkyl moiety has from 7 to 9 carbon atoms and is unsubstituted or has from 1 to 5, more preferably from 1 to 3, substituents selected from amino groups, C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups and hydroxy groups, for example the benzyloxycarbonyl, α-methylbenzyloxycarbonyl, phenethyloxycarbonyl, 3-phenylpropoxycarbonyl, 4-methoxybenzyloxycarbonyl, 4-hydroxybenzyloxycarbonyl, p -tolyloxycarbonyl and 4-aminobenzyloxycarbonyl groups. In addition to the acyl groups listed above, R² can also represent an acyl group derived from an amino acid by removal of OH from the carboxylic acid group and N -acylation of the amino group with at least one of the above-mentioned acyl groups. Hence, R² can also represent such an acyl group connected to the parent amino acid via one or more amino acid residues, preferably from 0 to 5, more preferably from 0 to 3 and most preferably from 0 to 2, such residues. Thus, R² could represent a group derived from an N -acylated amino acid, for example the N -benzoylglycyl or N -benzoylglycylglycyl group. Hence, compounds of general formula I also include such oligopeptide compounds as N -benzoylglycylglycine, N -benzoylglycylglycylglycine and similar compounds. Preferred examples of groups which may be represented by R² include: saturated aliphatic acyl groups having from 1 to 8 carbon atoms; aromatic acyl groups in which the aryl moiety has from 6 to 10 ring carbon atoms and is unsubstituted or has from 1 to 3 C₁-C₄ alkyl and/or C₁-C₄ alkoxy substituents; alicyclic acyl groups in which the cycloalkane ring has from 3 to 6 carbon atoms; araliphatic acyl groups in which the aryl ring has from 6 to 10 ring carbon atoms and the alkyl group has from 1 to 4 carbon atoms, the aryl ring being unsubstituted or having from 1 to 3 C₁-C₄ alkyl and/or C₁-C₄ alkoxy substituents; heterocyclic acyl groups in which the heterocyclic ring is saturated or unsaturated and has 5 or 6 ring atoms of which one is a nitrogen, sulphur or oxygen hetero-atom; alkoxycarbonyl groups having a total of from 2 to 7 carbon atoms; and aralkyloxycarbonyl groups in which the aralkyl moiety has from 7 to 9 carbon atoms and the aryl ring is unsubstituted or has from 1 to 3 C₁-C₄ alkyl and/or C₁-C₄ alkoxy substituents. Particularly preferred groups which may be represented by R² include: aromatic acyl groups in which the aryl ring has from 6 to 10 ring atoms and which is unsubstituted or has a single substituent selected from C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups, hydroxy groups and amino groups; alicyclic acyl groups in which the cycloalkane moiety has from 3 to 6 carbon atoms; phenylaliphatic acyl groups in which the phenyl group is unsubstituted or has a single C₁-C₄ alkyl substituent, and in which the alkyl part has from 1 to 4 carbon atoms; alkoxycarbonyl groups having a total of from 4 to 6 carbon atoms; and aralkyloxycarbonyl groups in which the aralkyl part has from 7 to 9 carbon atoms and has 0 or 1 C₁-C₄ alkyl or C₁-C₄ alkoxy substituent. In addition, such acyl groups linked to the amino acid via at least one further amino acid residue are preferred. Of the groups exemplified above, the following are most preferred: acetyl, benzoyl, cyclohexanecarbonyl, cyclopropanecarbonyl, hexanoyl, isobutyryl, crotonoyl, ethoxycarbonyl, 4-hydroxybenzoyl, anisoyl, 4-aminobenzoyl, naphthoyl, toluoyl, benzyloxycarbonyl and 4-methoxybenzyloxycarbonyl groups, of which the acetyl and benzoyl, particularly benzoyl, groups are most preferred. As explained previously, the lower alkanoyl groups, notably the acetyl group, are only most preferred in relation to their use with those amino acids which have relatively bulky and lipophilic groups. In the compounds of general formula II, X represents an alkylene group having from 1 to 10, preferably from 1 to 8 and more preferably from 1 to 5, carbon atoms. Such groups may have the "free" valencies attached to different carbon atoms or to the same carbon atom. In the latter case, the groups are sometimes referred to as "alkylidene" groups. Examples include the methylene, ethylidene, ethylene, propylidene, 1-methylethylidene, 1-methylethylene, trimethylene, butylidene, 2-methylpropylidene, 1-methylpropylidene, 1,2-dimethylethylene, 1-ethylethylene, 1-methyltrimethylene, 2-methyltrimethylene, tetramethylene, pentylidene, 3-methylbutylidene, 2-methylbutylidene, 2,2-dimethylpropylidene, 1-ethylpropylidene, 1,2-dimethylpropylidene, 1-propylethylene, 1-(1-methylethyl)ethylene, 1-ethyl-2-methylethylene, 1-ethyltrimethylene, 2-ethyltrimethylene, 1,3-dimethyltrimethylene, 1-methyltetramethylene, 2-methyltetramethylene, pentamethylene, hexylidene, 4-methylpentylidene, 3-methylpentylidene, 2-methylpentylidene, 1-methylpentylidene, 2-ethylbutylidene, 1-ethylbutylidene, 1,3-dimethylbutylidene, 1,2-dimethylbutylidene, 3,3-dimethylbutylidene, 2,3-dimethylbutylidene, 1-butylethylene, 1-methyl-2-propylethylene, 1,2-diethylethylene, 1-methyl-1-propylethylene, 2-propyltrimethylene, 1-ethyl-3-methyltrimethylene, 1-ethyltetramethylene, 2-ethyltetramethylene, 1,3-dimethyltetramethylene, 1-methylpentamethylene, 2-methylpentamethylene, 3-methylpentamethylene, hexamethylene, heptylidene, 5-methylhexylidene, 4-methylhexylidene, 3-methylhexylidene, 1-methylhexylidene, 3-ethylpentylidene, 1-ethylpentylidene, 4,4-dimethylpentylidene, 2,4-dimethylpentylidene, 1,2-dimethylpentylidene, 1-propylbutylidene, 2-ethyl-1-methylbutylidene, 1-ethyl-2-methylbutylidene, 1,2,2-trimethylbutylidene, 1,2,3-trimethylbutylidene, 1-pentylethylene, 1-butyl-2-methylethylene, 1-ethyl-2-propylethylene, 1-butyl-1-methylethylene, 1-ethyl-1-propylethylene, 1-butyltrimethylene, 2-butyltrimethylene, 1,3-diethyltrimethylene, 1-methyl-3-propyltrimethylene, 1-propyltetramethylene, 2-propyltetramethylene, 1-ethyl-4-methyltetramethylene, 3-ethyl-1-methyltetramethylene, 1-ethylpentamethylene, 3-ethylpentamethylene, 1,3-dimethylpentamethylene, 1-methylhexamethylene, 3-methylhexamethylene, heptamethylene, octylidene, 6-methylheptylidene, 4-methylheptylidene, 2-methylheptylidene, 1-methylheptylidene, 4-ethylhexylidene, 3-ethylhexylidene, 2-ethylhexylidene, 1-ethylhexylidene, 3,5-dimethylhexylidene, 4,5-dimethylhexylidene, 2,4-dimethylhexylidene, 1,5-dimethylhexylidene, 1,4-dimethylhexylidene, 2-propylpentylidene, 1-propylpentylidene, 2-ethyl-4-methylpentylidene, 3-ethyl-2-methylpentylidene, 3-ethyl-1-methylpentylidene, 1-ethyl-3-methylpentylidene, 3-methyl-1-propylbutylidene, 2-methyl-1-propyl-butylidene, 1-ethyl-2,3-dimethylbutylidene, 1,2-diethylbutylidene, 1-hexylethylene, 1-methyl-2-pentylethylene, 1-butyl-2-ethylethylene, 1,2-dipropylethylene, 1-pentyltrimethylene, 2-pentyltrimethylene, 1-butyl-3-methyltrimethylene, 1-butyl-2-methyltrimethylene, 1-ethyl-3-propyl-trimethylene, 1,2-dimethyl-3-propyltrimethylene, 1-butyltetramethylene, 1-methyl-4-propyltetramethylene, 1-propylpentamethylene, 3-propylpentamethylene, 2-ethyl-4-methylpentamethylene, 1-ethylhexamethylene, 3-ethylhexamethylene, 1,3-dimethylhexamethylene, 1-methylheptamethylene, 4-methylheptamethylene and octamethylene groups. The alkylene group represented by X, including those alkylene groups exemplified above, may be unsubstituted or may have at least 1, preferably from 1 to 4 and more preferably 1 or 2, substituents selected from the following groups: hydroxy groups; C₁-C₄ alkoxy groups, for example the methoxy or ethoxy groups; aryloxy groups in which the aryl ring has from 6 to 14, more preferably from 6 to 10, ring carbon atoms and which is unsubstituted or has from 1 to 5, more preferably from 1 to 3, substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups, for example the phenoxy, p -tolyloxy, 4-hydroxyphenoxy, 4-aminophenoxy and 4-methoxyphenoxy groups; C₇-C₉ aralkyloxy groups in which the aryl ring is unsubstituted or has from 1 to 5, more preferably from 1 to 3, substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups, for example the benzyloxy, 4-methylbenzyloxy, 4-hydroxybenzyloxy, 4-aminobenzyloxy and 4-methoxybenzyloxy groups; mercapto groups; C₁-C₄ alkylthio groups, for example the methylthio or ethylthio groups; arylthio groups in which the aryl ring has from 6 to 14, more preferably from 6 to 10, ring carbon atoms and which is unsubstituted or has from 1 to 5, more preferably from 1 to 3, substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups, for example the phenylthio, p -tolylthio, 4-hydroxyphenylthio, 4-aminophenylthio and 4-methoxyphenylthio groups; C₇-C₉ aralkylthio groups in which the aryl ring is unsubstituted or has from 1 to 5, more preferably from 1 to 3, substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups, for example the benzylthio, 4-methylbenzylthio, 4-hydroxybenzylthio, 4-aminobenzylthio and 4-methoxybenzylthio groups; carboxyalkylthio groups having from 1 to 4 carbon atoms in the alkyl moiety, for example the carboxymethylthio and carboxyethylthio groups; amino groups; amino groups having one or two C₁-C₄ alkyl substituents, for example the methylamino, ethylamino and dimethylamino groups; amino groups having one or two aryl substituents, wherein the aryl ring has from 6 to 14 ring carbon atoms and is unsubstituted or has from 1 to 5, preferably from 1 to 3, substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups, and C₁-C₄ alkoxy groups, such as the phenylamino, p -tolylamino, 4-hydroxyphenylamino, 4-aminophenylamino and 4-methoxyphenylamino groups; amino groups having one or two C₇-C₉ aralkyl substituents wherein the aryl moiety is unsubstituted or has from 1 to 5, preferably from 1 to 3, substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkyl groups, such as the benzylamino, 4-methylbenzylamino, 4-hydroxybenzylamino, 4-aminobenzylamino and 4-methoxybenzylamino groups; amino groups substituted by one or two carboxylic acyl groups as defined in relation to R²; aryl groups having from 6 to 14 ring carbon atoms, and being unsubstituted or having from 1 to 5, preferably from 1 to 3, substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; carboxy groups; amidino groups; sulpho groups; C₁-C₄ alkylsulphinyl groups, such as the methanesulphinyl or ethanesulphinyl groups; C₁-C₄ alkylsulphonyl groups, such as the methanesulphonyl or ethanesulphonyl groups; and heterocyclic groups, such as the pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolazinyl, indolyl and indazolyl groups. Preferred groups which may be represented by X include C₁-C₅ alkylene groups which are unsubstituted or have one or two substituents selected from: hydroxy groups; C₁-C₄ alkoxy groups; aryloxy groups wherein the aryl ring has from 6 to 14 ring carbon atoms and which is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; C₇-C₉ aralkyloxy groups, wherein the aryl moiety is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; mercapto groups; C₁-C₄ alkylthio groups; arylthio groups wherein the aryl ring has from 6 to 14 ring carbon atoms and which is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; C₇-C₉ aralkylthio groups wherein the aryl ring is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; carboxyalkylthio groups in which the alkyl part has from 1 to 4 carbon atoms; amino groups; amino groups having one or two C₁-C₄ alkyl substituents; amino groups having one or two aryl substituents in which the aryl ring has from 6 to 14 ring carbon atoms and is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; amino groups having one or two C₇-C₉ aralkyl substituents in which the aryl part is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; amino groups having one or two carboxylic acyl substituents as defined in relation to R²; aryl groups having from 6 to 14 ring carbon atoms and being unsubstituted or having from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; carboxy groups; and heterocyclic groups having from 5 to 9 ring atoms, of which from 1 to 3 are nitrogen and/or oxygen and/or sulphur hetero-atoms. More preferred groups which may be represented by X are C₁-C₅ alkylene groups which are unsubstituted or have 1 or 2 substituents selected from: hydroxy groups; C₁-C₄ alkoxy groups; mercapto groups; C₁-C₄ alkylthio groups; amino groups; amino groups having one or two C₁-C₄ alkyl substituents; amino groups having one or two carboxylic acyl substituents as defined for R²; aryl groups having from 6 to 14 carbon atoms wherein the aryl ring is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; carboxy groups; and heterocyclic groups having from 5 to 9 ring atoms, of which from 1 to 3 are nitrogen and/or oxygen hetero-atoms. Preferred amino acids which may be represented by general formula II include glycine, β-alanine, 4-aminobutyric acid, 5-aminovaleric acid, 6-aminohexanoic acid, 8-aminooctanoic acid, alanine, 2-aminobutyric acid, norvaline, valine, leucine, isoleucine, norleucine, tyrosine, O -methyltyrosine, aspartic acid, glutamic acid, 4-carboxyglutamic acid, 3-methylaspartic acid, 2-aminoadipic acid, 2-aminopimelic acid, 2-aminosuberic acid, 3-hydroxyaspartic acid, 3-hydroxyglutamic acid, 2,3-diaminopropionic acid, 2,4-diaminobutyric acid, 5-hydroxylysine, arginine, N δ , N δ -dimethylornithine, N ε -methyllysine, cysteine, methionine, ethionine, S -carboxymethylcysteine, S -benzylcysteine, methionine S -oxide, ethionine S -oxide, methionine S , S -dioxide, cysteic acid, serine, O -methylserine, threonine, O -methylthreonine, homothreonine, ethoxinine ( = 2-amino-4-ethoxybutyric acid), 3-methoxyvaline, 3-phenylserine, 3-methyl-3-phenylalanine, histidine, tryptophan, 2-methylalanine, 2-methylserine, 2-hydroxyisoleucine, 2-methylmethionine, 2-ethyl-2-phenylglycine, 3-aminobutyric acid, 3-amino-4-methylvaleric acid, 3-amino-3-phenylpropionic acid, 3-amino-2-hydroxypropionic acid and 4-amino-3-hydroxybutyric acid. More preferred amino acids are glycine, β-alanine, 4-aminobutyric acid, 5-aminovaleric acid, 6-aminohexanoic acid, 8-aminooctanoic acid, alanine, norvaline, valine, leucine, isoleucine, norleucine, N δ , N δ -dimethylornithine, methionine, ethionine, O -methylserine, O -methylthreonine, ethoxinine, 3-methoxyvaline, 3-phenylserine, 3-methyl-3-phenylalanine, histidine, 2-methylalanine, 2-methylserine, 2-hydroxyisoleucine, 2-ethylphenylglycine, 3-aminobutyric acid, 3-amino-4-methylvaleric acid and 3-amino-3-phenylpropionic acid. The most preferred amino acids are β-alanine, 4-aminobutyric acid, 5-aminovaleric acid, 6-aminohexanoic acid, alanine, valine, leucine, norleucine, methionine, histidine and glycine. When the amino acid derivative is an oligopeptide compound, such as a dipeptide or tripeptide, this type of compound is preferably formed by suitable combination of such amino acids as glycine, β-alanine, 4-aminobutyric acid, 5-aminovaleric acid, 6-aminohexanoic acid, alanine, valine, leucine, norleucine, phenylglycine, phenylalanine, methionine and histidine. Examples include leucylglycine, glycyl-β-alanine, glycylalanine, valylalanine, leucylalanine, glycylvaline, alanylvaline, leucylvaline, valylleucine, phenylalanylleucine, histidylleucine, glycylphenylalanine, alanylphenylalanine, leucylphenylalanine, glycylmethionine, valylmethionine, glycylhistidine, alanylvalylglycine, glycylalanylvaline, glycylphenylalanylleucine and glycylglycylhistidine. Specific examples of the amino acid compounds which may be employed in the present invention are given in the following list. It should, of course, be appreciated that these compounds can exist in the D -, L -and DL - forms and any of these forms can be employed. The compounds are hereinafter referred to by the numbers appended to them in this list. In the case of the amino acids having 2 or more amino groups (e.g. 2,3-diaminopropionic acid, 2,4-diaminobutyric acid and arginine), mono-acylated derivatives (in which the acyl group can be on any amino group) and polyacylated derivatives are possible. 1. Glycine derivatives. 1-1. N -hexanoylglycine 1-2. N -heptanoylglycine 1-3. N -octanoylglycine 1-4. N -nonanoylglycine 1-5. N -decanoylglycine 1-6. N -( p -toluoyl)glycine 1-7. N -(4-methoxybenzoyl)glycine 1-8. N -(1-naphthoyl)glycine 1-9. N -(1-phenyl-1-cyclohexanecarbonyl)glycine 1-10. N -(α,α-diphenylacetyl)glycine 1-11. N -(α-phenyl-α-cyclopentylacetyl)glycine 1-12. N -butoxycarbonylglycine 1-13. N -octanoylleucylglycine 1-14. N- -benzoylleucylglycine 1-15. N -butoxycarbonylleucylglycine 1-16. N -octanoylalanylvalylglycine 1-17. N -benzoylalanylvalylglycine 1-18. N -cyclohexanecarbonylalanylvalylglycine 1-19. N -butoxycarbonylalanylvalylglycine 2. β-Alanine derivatives 2-1. N -hexanoyl-β-alanine 2-2. N -heptanoyl-β-alanine 2-3. N -octanoyl-β-alanine 2-4. N -nonanoyl-β-alanine 2-5. N -( p -toluoyl)-β-alanine 2-6. N -(4-methoxybenzoyl)-β-alanine 2-7. N -(3-hydroxy-2-naphthoyl)-β-alanine 2-8. N -(1-phenyl-1-cyclopentanecarbonyl)-β-alanine 2-9. N -(α,α-diphenylacetyl)-β-alanine 2-10. N -(3-phenylpropionyl)-β-alanine 2-11. N -(4-phenylbutyryl)-β-alanine 2-12. N -(4-methoxyphenylacetyl)-β-alanine 2-13. N -t-butoxycarbonyl-β-alanine 2-14. N -benzyloxycarbonyl-β-alanine 2-15. N -(4-methoxybenzyloxycarbonyl)-β-alanine 2-16. N -(4-methylbenzyloxycarbonyl)-β-alanine 2-17. N -(α-methylbenzyloxycarbonyl)-β-alanine 2-18. N -benzoylglycyl-β-alanine 2-19. N -(1-naphthoyl)glycyl-β-alanine 2-20. N -cyclohexanecarbonylglycyl-β-alanine 2-21. N -benzyloxycarbonylglycyl-β-alanine 2-22. N -benzoyl-β-alanine 3. 4-Aminobutyric acid derivatives. 3-1. N -hexanoyl-4-aminobutyric acid 3-2. N -heptanoyl-4-aminobutyric acid 3-3. N -benzoyl-4-aminobutyric acid 3-4. N -( p -toluoyl)-4-aminobutyric acid 3-5. N -(3-methoxybenzoyl)-4-aminobutyric acid 3-6. N -cyclopentanecarbonyl-4-aminobutyric acid 3-7. N -cyclohexanecarbonyl-4-aminobutyric acid 3-8. N -(1-phenyl-1-cyclopropanecarbonyl)-4-aminobutyric acid 3-9. N -(1-phenyl-1-cyclopentanecarbonyl)-4-aminobutyric acid 3-10. N -phenylacetyl-4-aminobutyric acid 3-11. N -(3-phenylpropionyl)-4-aminobutyric acid 3-12. N -( p -tolylacetyl)-4-aminobutyric acid 3-13. N -nicotinoyl-4-aminobutyric acid 3-14. N -butoxycarbonyl-4-aminobutyric acid 3-15. N -benzyloxycarbonyl-4-aminobutyric acid 3-16. N -(3-phenylpropoxycarbonyl)-4-aminobutyric acid 3-17. N -(α-methylbenzyloxycarbonyl)-4-aminobutyric acid 3-18. N -(1-naphthoyl)-4-aminobutyric acid 4. 5-Aminovaleric acid derivatives 4-1. N -butyryl-5-aminovaleric acid 4-2. N -isobutyryl-5-aminovaleric acid 4-3. N -valeryl-5-aminovaleric acid 4-4. N -isovaleryl-5-aminovaleric acid 4-5. N -hexanoyl-5-aminovaleric acid 4-6. N -benzoyl-5-aminovaleric acid 4-7. N -( m -toluoyl)-5-aminovaleric acid 4-8. N -(2-methoxybenzoyl)-5-aminovaleric acid 4-9. N -cyclopentanecarbonyl-5-aminovaleric acid 4-10. N -cyclohexanecarbonyl-5-aminovaleric acid 4-11. N -(1-phenyl-1-cyclopropanecarbonyl)-5-aminovaleric acid 4-12. N -(1-phenyl-1-cyclohexanecarbonyl)-5-aminovaleric acid 4-13. N -phenylacetyl-5-aminovaleric acid 4-14. N -(α-phenyl-α-methylacetyl)-5-aminovaleric acid 4-15. N -nicotinoyl-5-aminovaleric acid 4-16. N -(2-thiophenecarbonyl)-5-aminovaleric acid 4-17. N -(2-furoyl)-5-aminovaleric acid 4-18. N -isopropoxycarbonyl-5-aminovaleric acid 4-19. N -pentyloxycarbonyl-5-aminovaleric acid 4-20. N -benzyloxycarbonyl-5-aminovaleric acid 4-21. N -(4-methoxybenzyloxycarbonyl)-5-aminovaleric acid 4-22. N -(4-methylbenzyloxycarbonyl)-5-aminovaleric acid 4-23. N -(4-hydroxyphenylacetyl)-5-aminovaleric acid 4-24. N ( N -methylnicotinoyl)-5-aminovaleric acid 5. 6-Aminohexanoic acid derivatives. 5-1. N -acetyl-6-aminohexanoic acid 5-2. N -propionyl-6-aminohexanoic acid 5-3. N -butyryl-6-aminohexanoic acid 5-4. N -isobutyryl-6-aminohexanoic acid 5-5. N -isovaleryl-6-aminohexanoic acid 5-6. N -hexanoyl-6-aminohexanoic acid 5-7. N -acryloyl-6-aminohexanoic acid 5-8. N -methacryloyl-6-aminohexanoic acid 5-9. N -crotonoyl-6-aminohexanoic acid 5-10. N -propioloyl-6-aminohexanoic acid 5-11. N -benzoyl-6-aminohexanoic acid 5-12. N -( o -toluoyl)-6-aminohexanoic acid 5-13. N -(4-methoxybenzoyl)-6-aminohexanoic acid 5-14. N -(4-aminobenzoyl)-6-aminohexanoic acid 5-15. N -(1-naphthoyl)-6-aminohexanoic acid 5-16. N -cyclobutanecarbonyl-6-aminohexanoic acid 5-17. N -cyclopentanecarbonyl-6-aminohexanoic acid 5-18. N -cyclohexanecarbonyl-6-aminohexanoic acid 5-19. N -phenylacetyl-6-aminohexanoic acid 5-20. N -(3-phenylpropionyl)-6-aminohexanoic acid 5-21. N -nicotinoyl-6-aminohexanoic acid 5-22. N -(2-thiophenecarbonyl)-6-aminohexanoic acid 5-23. N -methoxycarbonyl-6-aminohexanoic acid 5-24. N -ethoxycarbonyl-6-aminohexanoic acid 5-25. N -butoxycarbonyl-6-aminohexanoic acid 5-26. N -pentyloxycarbonyl-6-aminohexanoic acid 5-27. N -benzyloxycarbonyl-6-aminohexanoic acid 5-28. N -phenethyloxycarbonyl-6-aminohexanoic acid 5-29. N -(3-phenylpropoxycarbonyl)-6-aminohexanoic acid 5-30. N -(4-methoxybenzyloxycarbonyl)-6-aminohexanoic acid 5-31. N -(4-methylbenzyloxycarbonyl)-6-aminohexanoic acid 5-32. N -(α-methylbenzyloxycarbonyl)-6-aminohexanoic acid 5-33. N -( N -methylnicotinoyl)-6-aminohexanoic acid 5-34. N -(4-chlorophenylacetyl)-6-aminohexanoic acid 6. 8-Aminooctanoic acid derivatives. 6-1. N -acetyl-8-aminooctanoic acid 6-2. N -valeryl-8-aminooctanoic acid 6-3. N -benzoyl-8-aminooctanoic acid 6-4. N -(3-hydroxybenzoyl)-8-aminooctanoic acid 6-5. N -(3-sulphobenzoyl)-8-aminooctanoic acid 6-6. N -cyclopropanecarbonyl-8-aminooctanoic acid 6-7. N -(4-aminophenylacetyl)-8-aminooctanoic acid 6-8. N -methoxycarbonyl-8-aminooctanoic acid 6-9. N -propoxycarbonyl-8-aminooctanoic acid 6-10. N -isopropoxycarbonyl-8-aminooctanoic acid 6-11. N -benzyloxycarbonyl-8-aminooctanoic acid 6-12. N -(4-hydroxybenzyloxycarbonyl)-8-aminooctanoic acid 6-13. N -( N -methylnicotinoyl)-8-aminooctanoic acid 6-14. N -(6-hydroxynicotinoyl)-8-aminooctanoic acid 7. Alanine derivatives. 7-1. N -valerylalanine 7-2. N -hexanoylalanine 7-3. N -benzoylalanine 7-4. N -(4-methoxybenzoyl)alanine 7-5. N -(1-naphthoyl)alanine 7-6. N -(1-phenyl-1-cyclopropanecarbonyl)alanine 7-7. N -phenylacetylalanine 7-8. N -butoxycarbonylalanine 7-9. N -benzyloxycarbonylalanine 7-10. N -(α-methylbenzyloxycarbonyl)alanine 7-11. N -octanoylglycylalanine 7-12. N -benzoylglycylalanine 7-13. N -butoxycarbonylglycylalanine 7-14. N -benzoylvalylalanine 7-15. N -( p -toluoyl)valylalanine 7-16. N -cyclopentanecarbonylvalylalanine 7-17. N -cyclohexanecarbonylvalylalanine 7-18. N -benzyloxycarbonylvalylalanine 7-19. N -benzoylleucylalanine 7-20. N -(4-methoxybenzoyl)leucylalanine 7-21. N -butoxycarbonylleucylalanine 7-22. N -benzyloxycarbonylleucylalanine 7-23. N -(2-bromobenzoyl)alanine 8. 2-Aminobutyric acid derivatives. 8-1. N -pivaloyl-2-aminobutyric acid 8-2. N -hexanoyl-2-aminobutyric acid 8-3. N -heptanoyl-2-aminobutyric acid 8-4. N -benzoyl-2-aminobutyric acid 8-5. N -( p -toluoyl)-2-aminobutyric acid 8-6. N -(1-phenyl-1-cyclopentanecarbonyl)-2-aminobutyric acid 8-7. N -(α,α-diphenylacetyl)-2-aminobutyric acid 8-8. N -ethoxycarbonyl-2-aminobutyric acid 8-9. N -benzyloxycarbonyl-2-aminobutyric acid 8-10. N -(4-methoxybenzyloxycarbonyl-2-aminobutyric acid 9. Norvaline derivatives. 9-1. N -valerylnorvaline 9-2. N -decanoylnorvaline 9-3. N -benzoylnorvaline 9-4. N -( m -toluoyl)norvaline 9-5. N -(3-sulphobenzoyl)norvaline 9-6. N -cyclohexanecarbonylnorvaline 9-7. N -(1-phenyl-1-cyclohexanecarbonyl)norvaline 9-8. N -(α-phenyl-α-ethylacetyl)norvaline 9-9. N -(4-methoxyphenylacetyl)norvaline 9-10. N -(2-pyrazinecarbonyl)norvaline 9-11. N -benzyloxycarbonylnorvaline 9-12. N -(4-methylbenzyloxycarbonyl)norvaline 10. Valine derivatives. 10-1. N -propionylvaline 10-2. N -butyrylvaline 10-3. N -isobutyrylvaline 10-4. N -valerylvaline 10-5. N -acryloylvaline 10-6. N -methacryloylvaline 10-7. N -crotonoylvaline 10-8. N -propioloylvaline 10-9. N -(2-methoxybenzoyl)valine 10-10. N -(4-butoxybenzoyl)valine 10-11. N -cyclopentanecarbonylvaline 10-12. N -cyclohexanecarbonylvaline 10-13. N -(1-phenyl-1-cyclopentanecarbonyl)valine 10-14. N -phenylacetylvaline 10-15. N -nicotinoylvaline 10-16. N -(2-piperidinecarbonyl)valine 10-17. N -ethoxycarbonylvaline 10-18. N -isopropoxycarbonylvaline 10-19. N -t-butoxycarbonylvaline 10-20. N -pentyloxycarbonylvaline 10-21. N -benzyloxycarbonylvaline 10-22. N -( p -p-tolylacetyl)valine 10-23. N -benzoylglycylvaline 10-24. N -( p -toluoyl)glycylvaline 10-25. N -(1-naphthoyl)glycylvaline 10-26. N -cyclopentanecarbonylglycylvaline 10-27. N -butoxycarbonylglycylvaline 10-28. N -octanoylalanylvaline 10-29. N -benzoylalanylvaline 10-30. N -( p -toluoyl)alanylvaline 10-31. N -(4-aminobenzoyl)alanylvaline 10-32. N -(1-naphthoyl)alanylvaline 10-33. N -cyclohexanecarbonylalanylvaline 10-34. N -phenylacetylalanylvaline 10-35. N -benzyloxycarbonylalanylvaline 10-36. N -benzoylleucylvaline 10-37. N -benzoylglycylalanylvaline 10-38. N -( p -toluoyl)glycylalanylvaline 10-39. N -(1-naphthoyl)glycylalanylvaline 10-40. N -cyclopentanecarbonylglycylalanylvaline 10-41. N -butoxycarbonylglycylalanylvaline 10-42. N -benzyloxycarbonylglycylalanylvaline 10-43. N -( N -methylnicotinoyl)valine 10-44. N -(3-fluorobenzoyl)valine 10-45. N -benzoylvaline 11. Leucine derivatives. 11-1. N -butyrylleucine 11-2. N -isovalerylleucine 11-3. N -benzoylleucine 11-4. N -(4-butylbenzoyl)leucine 11-5. N -(2-hydroxybenzoyl)leucine 11-6. N -(3-sulphobenzoyl)leucine 11-7. N -cyclopentanecarbonylleucine 11-8. N -cyclohexanecarbonylleucine 11-9. N -(1-phenyl-1-cyclopropanecarbonyl)leucine 11-10. N -phenylacetylleucine 11-11. N -nicotinoylleucine 11-12. N -ethoxycarbonylleucine 11-13. N -benzyloxycarbonylleucine 11-14. N -(4-hydroxyphenylacetyl)leucine 11-15. N -benzoylvalylleucine 11-16. N -ethoxycarbonylvalylleucine 11-17. N -benzoylphenylalanylleucine 11-18. N -phenylacetylphenylalanylleucine 11-19. N -benzyloxycarbonylphenylalanylleucine 11-20. N -benzoylhistidylleucine 11-21. N -( p -toluoyl)histidylleucine 11-22. N -(4-hydroxybenzoyl)histidylleucine 11-23. N -(1-naphthoyl)histidylleucine 11-24. N -benzoylglycylphenylalanylleucine 11-25. N -(4-methoxybenzoyl)glycylphenylalanylleucine 11-26. N -phenylacetylglycylphenylalanylleucine 11-27. N -t-butoxycarbonylleucine 12. Isoleucine derivatives. 12-1. N -valerylisoleucine 12-2. N -pivaloylisoleucine 12-3. N -octanoylisoleucine 12-4. N -benzoylisoleucine 12-5. N -(3-hydroxybenzoyl)isoleucine 12-6. N -cyclopentanecarbonylisoleucine 12-7. N -cyclohexanecarbonylisoleucine 12-8. N -(1-phenyl-1-cyclopentanecarbonyl)isoleucine 12-9. N -phenylacetylisoleucine 12-10. N -methoxycarbonylisoleucine 12-11. N -propoxycarbonylisoleucine 12-12. N -isopropoxycarbonylisoleucine 12-13. N -benzyloxycarbonylisoleucine 13. Norleucine derivatives. 13-1. N -propionylnorleucine 13-2. N -valerylnorleucine 13-3. N -pivaloylnorleucine 13-4. N -nonanoylnorleucine 13-5. N -benzoylnorleucine 13-6. N -(4-hydroxybenzoyl)norleucine 13-7. N -cyclohexanecarbonylnorleucine 13-8. N -(1-phenyl-1-cyclopropanecarbonyl)norleucine 13-9. N -(α-phenyl-α-ethylacetyl)norleucine 13-10. N -ethoxycarbonylnorleucine 13-11. N -propoxycarbonylnorleucine 13-12. N -butoxycarbonylnorleucine 13-13. N -benzyloxycarbonylnorleucine 14. Oligopeptide derivatives 14-1. N -benzoylglycylphenylalanine 14-2. N -(4-hydroxybenzoyl)glycylphenylalanine 14-3. N -(1-naphthoyl)glycylphenylalanine 14-4. N -ethoxycarbonylglycylphenylalanine 14-5. N -benzyloxycarbonylglycylphenylalanine 14-6. N -benzoylalanylphenylalanine 14-7. N -( p -toluoyl)alanylphenylalanine 14-8. N -(4-hydroxybenzoyl)alanylphenylalanine 14-9. N -(4-aminobenzoyl)alanylphenylalanine 14-10. N -(1-naphthoyl)alanylphenylalanine 14-11. N -benzyloxycarbonylalanylphenylalanine 14-12. N -benzoylleucylphenylaline 14-13. N -(4-hydroxybenzoyl)leucyphenylalanine 14-14. N -cyclohexanecarbonylleucylphenylalanine 14-15. N -benzyloxycarbonylleucylphenylalanine 15. Tyrosine derivatives. 15-1. N -benzoyltyrosine 15-2. N -(3-methoxybenzoyl)tyrosine 15-3. N -cyclohexanecarbonyltyrosine 15-4. N -benzyloxycarbonyltyrosine 15-5. N -phenethyloxycarbonyltyrosine 16. O-Methyltyrosine derivatives. 16-1. N -acetyl- O -methyltyrosine 16-2. N -propioloyl- O -methyltyrosine 16-3. N -benzoyl- O -methyltyrosine 16-4. N -(4-aminobenzoyl)- O -methyltyrosine 16-5. N -(1-phenyl-1-cyclopentanecarbonyl)- O -methyltyrosine 16-6. N -(1-phenyl-1-cyclohexanecarbonyl)- O -methyltyrosine 16-7. N -methoxycarbonyl- O -methyltyrosine 16-8. N -benzyloxycarbonyl- O -methyltyrosine 16-9. N -phenethyloxycarbonyl- O -methyltyrosine 17. Aspartic acid derivatives. 17-1. N -heptanoylaspartic acid 17-2. N -decanoylaspartic acid 17-3. N -(4-hydroxybenzoyl)aspartic acid 17-4. N -(3-hydroxy-2-naphthoyl)aspartic acid 17-5. N -(1-phenyl-1-cyclopentanecarbonyl)aspartic acid 17-6. N -(1-phenyl-1-cyclohexanecarbonyl)aspartic acid 17-7. N -benzyloxycarbonylaspartic acid 17-8. N -(4-methoxybenzyloxycarbonyl)aspartic acid 18. Glutamic acid derivatives. 18-1. N -nonanoylglutamic acid 18-2. N -(4-methoxybenzoyl)glutamic acid 18-3. N -(1-naphthoyl)glutamic acid 18-4. N -(1-phenyl-1-cyclopentanecarbonyl)glutamic acid 18-5. N -benzyloxycarbonylglutamic acid 18-6. N -benzoylglutamic acid 19. 4-Carboxyglutamic acid derivatives. 19-1. N -heptanoyl-4-carboxyglutamic acid 19-2. N -(4-methoxybenzoyl)-4-carboxyglutamic acid 19-3. N -(1-naphthoyl)-4-carboxyglutamic acid 19-4. N -(1-hydroxy-2-naphthoyl)-4-carboxyglutamic acid 19-5. N -phenylacetyl-4-carboxyglutamic acid 20. 3-Methylaspartic acid derivatives. 20-1. N -octanoyl-3-methylaspartic acid 20-2. N -(4-methoxybenzoyl)-3-methylaspartic acid 20-3. N -(α-phenyl-α-cyclopentylacetyl)-3-methylaspartic acid 21. 2-Aminoadipic acid derivatives. 21-1. N -hexanoyl-2-aminoadipic acid 21-2. N -benzoyl-2-aminoadipic acid 21-3. N -( p -toluoyl)-2-aminoadipic acid 21-4. N -(1-naphthoyl)-2-aminoadipic acid 21-5. N -(4-phenylbutyryl)-2-aminoadipic acid 21-6. N -phenylacetyl-2-aminoadipic acid 21-7. N -ethoxycarbonyl-2-aminoadipic acid 22. 2-Aminopimelic acid derivatives. 22-1. N -valeryl-2-aminopimelic acid 22-2. N -benzoyl-2-aminopimelic acid 22-3. N -(3-phenylpropionyl)-2-aminopimelic acid 22-4. N -methoxycarbonyl-2-aminopimelic acid 22-5. N -ethoxycarbonyl-2-aminopimelic acid 22-6. N -benzyloxycarbonyl-2-aminopimelic acid 23. 2-Aminosuberic acid derivatives. 23-1. N -butyryl-2-aminosuberic acid 23-2. N -benzoyl-2-aminosuberic acid 23-3. N -(1-naphthoyl)-2-aminosuberic acid 23-4. N -(α-phenyl-α-cyclopentylacetyl)-2-aminosuberic acid 23-5. N -methoxycarbonyl-2-aminosuberic acid 23-6. N -propoxycarbonyl-2-aminosuberic acid 24. 3-Hydroxyaspartic acid derivatives. 24-1. N -(1-naphthoyl)-3-hydroxyaspartic acid 24-2. N -(1-phenyl-1-cyclohexanecarbonyl)-3-hydroxyaspartic acid 24-3. N -(α-phenyl-α-ethylacetyl)-3-hydroxyaspartic acid 25. 3-Hydroxyglutamic acid derivatives. 25-1. N -(1-naphthoyl)-3-hydroxyglutamic acid 25-2. N -(1-phenyl-1-cyclohexanecarbonyl)-3-hydroxyglutamic acid 25-3. N -(α,α-diphenylacetyl)-3-hydroxyglutamic acid 26. 2,3-Diaminopropionic acid derivatives. 26-1. N α -hexanoyl-2,3-diaminopropionic acid 26-2. N α -(4-butylbenzoyl)-2,3-diaminopropionic acid 26-3. N α , N β -dibenzoyl-2,3-diaminopropionic acid 26-4. N α -(1-phenyl-1-cyclopentanecarbonyl)-2,3-diaminopropionic acid 26-5. N α -(α-phenyl-α-ethylacetyl)-2,3-diaminopropionic acid 27. 2,4-Diaminobutyric acid derivatives. 27-1. N α -(1-naphthoyl)-2,4-diaminobutyric acid 27-2. N α , N γ -dibenzoyl-2,4-diaminobutyric acid 27-3. N α -(1-phenyl-1-cyclopentanecarbonyl)-2,4-diaminobutyric acid 27-4. N α -(α-phenyl-α-ethylacetyl)-2,4-diaminobutyric acid 28. 5-Hydroxylysine derivatives. 28-1. N α -( p -toluoyl)-5-hydroxylysine 28-2. N α , N δ -dibenzoyl-5-hydroxylysine 28-3. N α -(1-phenyl-1-cyclopentanecarbonyl)-5-hydroxylysine 28-4. N α -(α-phenyl-α-cyclopentylacetyl)-5-hydroxylysine 28-5. N α -(1-phenyl-1-cyclopentanecarbonyl)-5-hydroxylysine 29. Arginine derivatives. 29-1. N α -heptanoylarginine 29-2. N α -(2-methoxybenzoyl)arginine 30. N δ ,N δ -Dimethylornithine derivatives. 30-1. N α -pivaloyl- N δ , N δ -dimethylornithine 30-2. N α -octanoyl- N δ , N δ -dimethylornithine 30-3. N α -acryloyl- N δ , N δ -dimethylornithine 30-4. N α -benzoyl- N δ , N δ -dimethylornithine 30-5. N α -(4-hydroxybenzoyl)- N δ , N δ -dimethylornithine 30-6. N α -cyclohexanecarbonyl- N δ , N δ -dimethylornithine 30-7. N α -(α-phenyl-α-methylacetyl)- N δ , N δ -dimethylornithine 30-8. N α -ethoxycarbonyl- N α , N α -dimethylornithine 30-9. N α -butoxycarbonyl- N δ , N δ -dimethylornithine 30-10. N α -benzyloxycarbonyl- N δ , N δ -dimethylornithine 31. N ε -Methyllysine derivatives. 31-1. N α -hexanoyl- N ε -methyllysine 31-2. N α -nonanoyl- N ε -methyllysine 31-3. N α -acryloyl- N ε -methyllysine 31-4. N α -benzoyl- N ε -methyllysine 31-5. N α -(4-butoxybenzoyl)- N ε -methyllysine 31-6. N α -(3-sulphobenzoyl)- N ε -methyllysine 31-7. N α -cyclobutanecarbonyl- N ε -methyllysine 31-8. N α -cyclohexanecarbonyl- N ε -methyllysine 31-9. N α -phenylacetyl- N ε -methyllysine 31-10. N α -propoxycarbonyl- N ε -methyllysine 31-11. N α -isopropoxycarbonyl- N ε -methyllysine 31-12. N α -benzyloxycarbonyl- N ε -methyllysine 32. Cysteine derivatives. 32-1. N -phenylacetylcysteine 33. Methionine derivatives. 33-1. N -valerylmethionine 33-2. N -acryloylmethionine 33-3. N -methacryloylmethionine 33-4. N -benzoylmethionine 33-5. N -( p -toluoyl)methionine 33-6. N -(4-methoxybenzoyl)methionine 33-7. N -(4-aminobenzoyl)methionine 33-8. N -cyclopentanecarbonylmethionine 33-9. N -cyclohexanecarbonylmethionine 33-10. N- -(1-phenyl-1-cyclohexanecarbonyl)methionine 33-11. N -phenylacetylmethionine 33-12. N -(α-phenyl-α-methylacetyl)methionine 33-13. N -methoxycarbonylmethionine 33-14. N -ethoxycarbonylmethionine 33-15. N -butoxycarbonylmethionine 33-16. N -benzyloxycarbonylmethionine 33-17. N -(4-methylbenzyloxycarbonyl)methionine 33-18. N -benzoylglycylmethionine 33-19. N -(4-methoxybenzoyl)glycylmethionine 33-20. N -benzyloxycarbonylglycylmethionine 33-21. N -benzoylvalylmethionine 33-22. N -cyclopentanecarbonylvalylmethionine 33-23. N -ethoxycarbonylvalylmethionine 34. Ethionine derivatives. 34-1. N -butyrylethionine 34-2. N -benzoylethionine 34-3. N -(p-toluoyl)ethionine 34-4. N -( m -toluoyl)ethionine 34-5. N -(4-butylbenzoyl)ethionine 34-6. N -(4-hydroxybenzoyl)ethionine 34-7. N -(4-aminobenzoyl)ethionine 34-8. N -(3-sulphobenzoyl)ethionine 34-9. N -(1-phenyl-1-cyclopropanecarbonyl)ethionine 34-10. N -phenylacetylethionine 34-11. N -methoxycarbonylethionine 34-12. N -ethoxycarbonylethionine 34-13. N -benzyloxycarbonylethionine 34-14. N -(4-methoxybenzyloxycarbonyl)ethionine 34-15. N -cyclohexanecarbonylethionine 35. S-Carboxymethylcysteine derivatives. 35-1. N -propionyl- S -carboxymethylcysteine 35-2. N -acryloyl- S -carboxymethylcysteine 35-3. N -benzoyl- S -carboxymethylcysteine 35-4. N -( p -toluoyl)- S -carboxymethylcysteine 35-5. N -(4-methoxybenzoyl)- S -carboxymethylcysteine 35-6. N -(4-butoxybenzoyl)- S -carboxymethylcysteine 35-7. N -cyclohexanecarbonyl- S -carboxymethylcysteine 35-8. N -(1-phenyl-1-cyclopentanecarbonyl)- S -carboxymethylcysteine 35-9. N -(α-methylbenzyloxycarbonyl)- S -carboxymethylcysteine 36. S-Benzylcysteine derivatives. 36-1. N -benzoyl- S -benzylcysteine 36-2. N -(4-hydroxybenzoyl)- S -benzylcysteine 36-3. N -(3-sulphobenzoyl)- S -benzylcysteine 36-4. N -cyclopropanecarbonyl- S -benzylcysteine 36-5. N -methoxycarbonyl- S -benzylcysteine 36-6. N -ethoxycarbonyl- S -benzylcysteine 36-7. N -propoxycarbonyl- S -benzylcysteine 36-8. N -(4-hydroxybenzyloxycarbonyl)- S -benzylcysteine 37. Methionine S-oxide derivatives. 37-1. N -( p -toluoyl)methionine S -oxide 37-2. N -pentyloxycarbonylmethionine S -oxide 37-3. N -benzyloxycarbonylmethionine S -oxide 38. Ethionine S-oxide derivatives. 38-1. N -benzoylethionine S -oxide 38-2. N -benzyloxycarbonylethionine S -oxide 39. Methionine S,S-dioxide derivatives. 39-1. N -(1-napthoyl)methionine S , S -dioxide 39-2. N cyclohexanecarbonylmethionine S , S -dioxide 39-3. N -pentyloxycarbonylmethionine S , S -dioxide 40. Cysteic acid derivatives. 40-1. N -( p- toluoyl)cysteic acid 40-2. n -(1-napthoyl)cysteic acid 40-3. N -(3-hydroxy-2-napthoyl)cysteic acid 40-4. N -(1-phenyl-1-cyclohexanecarbonyl)cysteic acid 41. Serine derivatives. 41-1. N -octanoylserine 41-2. N -benzoylserine 41-3. N -( m -toluoyl)serine 41-4. N -(4-methoxybenzoyl)serine 41-5. N -(1-napthoyl)serine 41-6. N -(1-phenyl-1-cyclopentanecarbonyl)serine 41-7. N -benzyloxycarbonylserine 41-8. N -(α-methylbenzyloxycarbonyl)serine 42. O-methylserine derivatives. 42-1. N -valeryl- O -methylserine 42-2. N -benzoyl- O -methylserine 42-3. N -cyclohexanecarbonyl- O -methylserine 42-4. N -phenylacetyl-O-methylserine 42-5. N -(α-phenyl-α-methylacetyl)- O -methylserine 42-6. N -(3-phenylpropionyl)- O -methylserine 42-7. N -phenethyloxycarbonyl- O -methylserine 43. Threonine derivatives. 43-1. N -hexanoylthreonine 43-2. N -nonanoylthreonine 43-3. N -benzoylthreonine 43-4. N -(3-hydroxy-2-naphthoyl)threonine 43-5. N -cyclohexanecarbonylthreonine 43-6. N -(α,α-diphenylacetyl)threonine 43-7. N -butoxycarbonylthreonine 43-8. N -benzyloxycarbonylthreonine 43-9. N -(4-methoxybenzyloxycarbonyl)threonine 44. O-Methylthreonine derivatives. 44-1. N -butyryl- O -methylthreonine 44-2. N -(4-methoxybenzyoyl)- O -methylthreonine 44-3. N -(1-naphthoyl)- O -methylthreonine 44-4. N -(1-phenyl-1-cyclopentanecarbonyl)- O -methylthreonine 44-5. N -ethyoxycarbonyl- O -methylthreonine 44-6. N -(3-phenylpropoxycarbonyl)- O -methylthreonine 45. Homoserine derivatives. 45-1. N -heptanoylhomoserine 45-2. N -benzoylhomoserine 45-3. N -(3-methoxybenzoyl)homoserine 45-4. N -(α-phenyl-α-cyclopentylacetyl)homoserine 45-5. N -(4-hydroxybenzyloxycarbonyl)homoserine 45-6. N -(4-methylbenzyloxycarbonyl)homoserine 46. Ethoxinine derivatives. 46-1. N -benzoylethoxinine 46-2. N -(4-butoxybenzoyl)ethoxinine 46-3. N -cyclohexanecarbonylethoxinine 46-4. N -methoxycarbonylethoxinine 47. 3-Methoxyvaline derivatives. 47-1. N -isovaleryl-3-methoxyvaline 47-2. N -(p-toluoyl)-3-methoxyvaline 47-3. N -(1-naphthoyl)-3-methoxyvaline 47-4. N -cyclopentanecarbonyl-3-methoxyvaline 47-5. N -cyclohexanecarbonyl-3-methoxyvaline 47-6. N -methoxycarbonyl-3-methoxyvaline 47-7. N -ethoxycarbonyl-3-methoxyvaline 48. 3-Phenylserine derivatives. 48-1. N -propionyl-3-phenylserine 48-2. N -(4-aminobenzoyl)-3-phenylserine 48-3. N -(1-naphthoyl)-3-phenylserine 48-4. N -benzoyl-3-phenylserine 48-5. N -cyclohexanecarbonyl-3-phenylserine 48-6. N -phenylacetyl-3-phenylserine 48-7. N -methoxycarbonyl-3-phenylserine 48-8. N -butoxycarbonyl-3-phenylserine 48-9. N -benzyloxycarbonyl-3-phenylserine 48-10. N -(α-methylbenzyloxycarbonyl)-3-phenylserine 49. 3-Methyl-3-phenylalanine derivatives. 49-1. N -acetyl-3-methyl-3-phenylalanine 49-2. N -hexanoyl-3-methyl-3-phenylalanine 49-3. N -benzoyl-3-methyl-3-phenylalanine 49-4. N -(4-aminobenzoyl)-3-methyl-3-phenylalanine 49-5. N -(3-sulphobenzoyl)-3-methyl-3-phenylalanine 49-6. N -cyclobutanecarbonyl-3-methyl-3-phenylalanine 49-7. N -cyclopentanecarbonyl-3-methyl-3-phenylalanine 49-8. N -phenylacetyl-3-methyl-3-phenylalanine 49-9. N -isopropoxycarbonyl-3-methyl-3-phenylalanine 49-10. N -butoxycarbonyl-3-methyl-3-phenylalanine 49-11. N -(4-aminobenzyloxycarbonyl)-3-methyl-3-phenylalanine 50. Histidine derivatives. 50-1. N -acetylhistidine 50-2. N -hexanoylhistidine 50-3. N -acryloylhistidine 50-4. N -methacryloylhistidine 50-5. N -benzoylhistidine 50-6. N -( p -toluoyl)histidine 50-7. N -(4-methoxybenzoyl)histidine 50-8. N -(4-butoxybenzoyl)histidine 50-9. N -cyclopentanecarbonylhistidine 50-10. N -cyclohexanecarbonylhistidine 50-11. N -(1-phenyl-1-cyclopentanecarbonyl)histidine 50-12. N -phenylacetylhistidine 50-13. N -(α-phenyl-α-cyclopentylacetyl)histidine 50-14. N -(4-methoxybenzyloxycarbonyl)histidine 50-15. N -benzoylglycylhistidine 50-16. N -(4-butylbenzoyl)glycylhistidine 50-17. N -phenylacetylglycylhistidine 50-18. N -ethoxycarbonylglycylhistidine 50-19. N -benzyloxycarbonylglycylhistidine 50-20. N -benzoylglycylglyclhistidine 50-21. N -ethoxycarbonylglycylglycylhistidine 50-22. N -benzyloxycarbonylglycylglycylhistidine 50-23. N -t-butoxycarbonylhistidine 51. Tryptophan derivatives. 51-1. N -(4-hydroxybenzoyl)tryptophan 51-2. N -benzyloxycarbonyltryptophan 52. 2-Methylalanine derivatives. 52-1. N -propionyl-2-methylalanine 52-2. N -benzoyl-2-methylalanine 52-3. N -( m -toluoyl)-2-methylalanine 52-4. N -(3-methoxybenzoyl)-2-methylalanine 52-5. N -cyclobutanecarbonyl-2-methylalanine 52-6. N -phenylacetyl-2-methylalanine 52-7. N -phenethyloxycarbonyl-2-methylalanine 53. 2-Methylserine derivatives. 53-1. N -valeryl-2-methylserine 53-2. N -octanoyl-2-methylserine 53-3. N -benzoyl-2-methylserine 53-4. N -( o -toluoyl)-2-methylserine 53-5. N -(4-methoxybenzoyl)-2-methylserine 53-6. N -(1-naphthoyl)-2-methylserine 53-7. N -cyclopentanecarbonyl-2-methylserine 53-8. N -(α,α-diphenylacetyl)-2-methylserine 53-9. N -pentyloxycarbonyl-2-methylserine 54. 2-Hydroxyisoleucine derivatives. 54-1. N -valeryl-2-hydroxyisoleucine 54-2. N -heptanoyl-2-hydroxyisoleucine 54-3. N -benzoyl-2-hydroxyisoleucine 54-4. N -(4-butylbenzoyl)-2-hydroxyisoleucine 54-5. N -(3-hydroxy-2-naphthoyl)-2-hydroxyisoleucine 54-6. N -cyclohexanecarbonyl-2-hydroxyisoleucine 54-7. N -phenylacetyl-2-hydroxyisoleucine 55. 2-Methylmethionine derivatives. 55-1. N -hexanoyl-2-methylmethionine 55-2. N -benzoyl-2-methylmethionine 55-3. N -(4-hydroxybenzoyl)-2-methylmethionine 55-4. N -propoxycarbonyl-2-methylmethionine 55-5. N -isopropoxycarbonyl-2-methylmethionine 56. 2-Ethyl-2-phenylglycine derivatives. 56-1. N -acetyl-2-ethyl-2-phenylglycine 56-2. N -butyryl-2-ethyl-2-phenylglycine 56-3. N -(3-sulphobenzoyl)-2-ethyl-2-phenylglycine 56-4. N -ethoxycarbonyl-2-ethyl-2-phenylglycine 56-5. N -propoxycarbonyl-2-ethyl-2-phenylglycine 57. 3-Aminobutyric acid derivatives. 57-1. N -hexanoyl-3-aminobutyric acid 57-2. N -benzoyl-3-aminobutyric acid 57-3. N -(4-methoxybenzoyl)-3-aminobutyric acid 57-4. N -(3-sulphobenzoyl)-3-aminobutyric acid 57-5. N -(1-naphthoyl)-3-aminobutyric acid 57-6. N -cyclopropanecarbonyl-3-aminobutyric acid 57-7. N -(α,α-diphenylacetyl)-3-aminobutyric acid 57-8. N -(4-phenylbutyl)-3-aminobutyric acid 57-9. N -(α-methylbenzyloxycarbonyl)-3-aminobutyric acid 58. 3-Amino-4-methylvaleric acid derivatives. 58-1. N -valeryl-3-amino-4-methylvaleric acid 58-2. N -isovaleryl-3-amino-4-methylvaleric acid 58-3. N -heptanoyl-3-amino-4-methylvaleric acid 58-4. N -benzoyl-3-amino-4-methylvaleric acid 58-5. N -( m -toluoyl)-3-amino-4-methylvaleric acid 58-6. N -(3-sulphobenzoyl)-3-amino-4-methylvaleric acid 58-7. N -(1-naphthoyl)-3-amino-4-methylvaleric acid 58-8. N -phenylacetyl-3-amino-4-methylvaleric acid 58-9. N -(3-phenylpropionyl)-3-amino-4-methylvaleric acid 58-10. N -butoxycarbonyl-3-amino-4-methylvaleric acid 58-11. N -(4-methylbenzyloxycarbonyl)-3-amino-4-methylvaleric acid 59. 3-Amino-3-phenylpropionic acid derivatives. 59-1. N -butyryl-3-amino-3-phenylpropionic acid 59-2. N -valeryl-3-amino-3-phenylpropionic acid 59-3. N -benzoyl-3-amino-3-phenylpropionic acid 59-4. N -(4-aminobenzoyl)-3-amino-3-phenylpropionic acid 59-5. N -cyclopropanecarbonyl-3-amino-3-phenylpropionic acid 59-6. N -cyclobutanecarbonyl-3-amino-3-phenylpropionic acid 59-7. N -cyclopentanecarbonyl-3-amino-3-phenylpropionic acid 59-8. N -methoxycarbonyl-3-amino-3-phenylpropionic acid 59-9. N -propoxycarbonyl-3-amino-3-phenylpropionic acid 59-10. N -butoxycarbonyl-3-amino-3-phenylpropionic acid 59-11. N -(4-aminobenzyloxycarbonyl)-3-amino-3-phenyl-propionic acid 60. 3-Amino-2-hydroxypropionic acid derivatives. 60-1. N -valeryl-3-amino-2-hydroxypropionic acid 60-2. N -heptanoyl-3-amino-2-hydroxypropionic acid 60-3. N -benzoyl-3-amino-2-hydroxypropionic acid 60-4. N -(3-methoxybenzoyl)-3-amino-2-hydroxypropionic acid 60-5. N -cyclohexanecarbonyl-3-amino-2-hydroxypropionic acid 60-6. N -benzyloxycarbonyl-3-amino-2-hydroxypropionic acid 60-7. N -(3-phenylpropoxycarbonyl)-3-amino-2-hydroxypropionic acid 61. 4-Amino-3-hydroxybutyric acid derivatives 61-1. N -isobutyryl-4-amino-3-hydroxybutyric acid 61-2. N -decanoyl-4-amino-3-hydroxybutyric acid 61-3. N -benzoyl-4-amino-3-hydroxybutyric acid 61-4. N -( o -toluoyl)-4-amino-3-hydroxybutyric acid 61-5. N -(3-aminobenzoyl)-4-amino-3-hydroxybutyric acid 61-6. N -(1-phenyl-1-cyclohexanecarbonyl)-4-amino-3-hydroxybutyric acid 61-7. N -(α-phenyl-α-methylacetyl)-4-amino-3-hydroxybutyric acid 61-8. N -(4-methoxybenzyloxycarbonyl)-4-amino-3-hydroxybutyric acid Of the amino acid derivatives listed above, the following are particularly preferred: Compounds No. 2-5, 2-6, 2-7, 2-18, 2-22, 4-6, 5-11, 5-18, 5-33, 6-3, 7-3, 7-5, 7-14, 8-4, 9-3, 10-4, 10-29, 10-45, 11-3, 11-24, 13-5, 14-1, 14-6, 14-14, 16-3, 33-4, 33-11, 33-21, 34-2, 34-14, 43-3, 50-5, 50-6, 50-7, 57-3 and 59-1. Of these, Compounds No. 2-22 and 10-45, especially No. 2-22, are most preferred. The amino acid derivatives employed in the present invention are acids and, as such, are capable of forming salts; any pharmaceutically acceptable salt of these amino acids may be employed. Examples of such salts include: alkali metal salts such as the sodium or potassium salts; alkaline earth metal salts, such as the calcium salt; other metal salts, such as the magnesium, aluminium, iron, zinc, copper, nickel and cobalt salts; the ammonium salt; and salts with amino sugars, such as glucosamine and galactosamine. The compositions of the invention may be prepared by any suitable method which involves mixing the antibiotic with the amino acid derivative and the invention is not intended to be limited by any particular method of preparation. Since the amino acid derivatives employed in this invention have, in general, very limited solubility in water, it is preferred that they should first be dispersed in water and then converted to a suitable salt by adding an aqueous solution of an appropriate base, for example: a metal compound, such as sodium hydroxide or potassium hydroxide; ammonia; or an amino sugar, such as glucosamine or galactosamine. Sufficient of the base is preferably added to adjust the pH of the mixture to a value within the range from 5.5 to 9, more preferably from 6 to 9. The penem or carbapenem antibiotic is then added to the resulting solution. The mixed solution thus obtained may be employed as such or it may first be lyophilized to give a powdery mixture, which may be subsequently formulated into an appropriate dosage form suitable for the chosen route of administration, either by the manufacturer or prior to use. The above mixing and preparation steps may take place at any temperature at which the components are fluid (especially the media) and are not decomposed, e.g. from 0 to 100°C, more conveniently from 0 to 50°C and most conveniently at about ambient temperature. Although it is convenient to administer the antibiotic and the amino acid derivative simultaneously in a single composition, it is, of course, clear that the two compounds may be administered separately, provided that they are administered sufficiently closely in time to each other that the amino acid derivative has a suitable concentration in the blood for all or most of the time that the antibiotic is present. Normally, it is anticipated that this will be achieved if the two compounds are administered within about one hour of each other, the amino acid preferably being administered before the antibiotic. The composition of the invention is particularly suitable for use by intravenous administration. There is no particular restriction on the relative proportions of the amino acid derivative and the penem or carbapenem antibiotic; in general, we have found that weight proportions of amino acid derivative to antibiotic of from 0.1:1 to 4:1 give good results, but equally proportions outside this range may successfully be employed. Approximately equal weights are generally most convenient. The invention is further illustrated by the following Examples and Activity Tests. In the following, the penem or carbapenem antibiotics are referred to by the numbers appended to them in the foregoing list and are identified as "(Carba)-Penem Cpd No" whilst the amino acid derivatives are also identified by the numbers appended to them in the foregoing list and are referred to as "Amino Acid Cpd No." EXAMPLE 1 5 g of N -benzoylvaline (Amino Acid Compound No. 10-45) were weighed out and dispersed in 80 ml of water. A 1N aqueous solution of sodium hydroxide was slowly added to this dispersion, and dissolved the N -benzoylvaline when the pH of the solution reached a value of 7-8. Then, 5 g of (5 R ,6 S )-2-[(3 S )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (Carbapenem Compound No. 6) were dissolved in this solution, to give a total volume of 100 ml. EXAMPLE 2 5 g of N -benzoyl-β-alanine (Amino Acid Compound No. 2-22) were weighed out and dispersed in 40 ml of water. A 1N aqueous solution of sodium hydroxide was slowly added to this dispersion, and dissolved the N -benzoyl-β-alanine when the pH of the solution reached a value of 7-8. Then, 5 g of (5 R ,6 S )-2-[3 S )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (Carbapenem Compound No. 6) were dissolved in this solution, to give a total volume of 50 ml. EXAMPLE 3 Similar procedures to those described in Examples 1 and 2 were carried out, using the other penem or carbapenem antibiotic substances and the other acylated amino acid derivatives shown in the following Table, in the amounts shown in that Table. In this Table, where the amino acid derivatives are not specified as being D - or L -, then they are the DL -form. ACTIVITY TESTS The preparation obtained by the procedure described in Example 1 was injected into the ear vein of a rabbit (about 3 kg body weight) in an amount of 3 ml/kg [that is 150 mg/kg of the Carbapenem Compound No.6 + 150 mg/kg of N -benzoylvaline (Amino Acid Compound No. 10-45)]. A preparation which had been obtained by the same procedure as that described in Example 1 but not including the N -benzoylvaline was injected into another rabbit, as a control, in a similar manner to the above. After one week, the kidneys of both rabbits were excised and examined. A change was observed in the renal tissue of the rabbits to which had been administered the preparation without the N -benzoylvaline, but no such change at all was observed in the renal tissue of rabbits to which had been administered the preparation containing the N -benzoylvaline. Similar experiments were carried out on other preparations which were prepared from other penem or carbapenem antibiotic substances and other amino acid derivatives. The Table also shows the results of these experiments. The observed change in the renal tissue of the control rabbits was a degenerative necrosis of the proximal renal tubules in the region of the renal cortex. In the following Table, where the proportion of the total area of this region which exhibited such necrosis was from 0 to 25%, this is shown as +++. Where the area is less than 50% this is shown as ++ and where it is less than 75% this is shown as +. Where different animals within each test group exhibited different responses, this is shown as e.g. +++ - ++ or ++ - +. It should be noted that, whenever penem or carbapenem antibiotic substances which were not combined with amino acid derivatives were administered, a change in the renal tissue was observed. Hence, all of the experiments carried out (even where the effect is only "+") demonstrated a significant protective effect of the amino acid derivative.

Claims: Claims for the following Contracting States : GB, DE, FR, IT, CH, BE, NL, SE, LU A composition comprising: a penem or carbapenem antibiotic; and a pharmaceutically acceptable N -acylated derivative of an amino acid wherein the amino group and the carboxylic acid group are attached to a saturated aliphatic carbon chain or carbon atom, or a salt thereof, provided that, where the composition comprises only one amino acid derivative, the amino acid is not ornithine, lysine, phenylalanine or phenylglycine, the amount of amino acid derivative being sufficient to alleviate any renal toxicity or the antibiotic, preferably in a weight ratio of said N -acylated amino acid to said antibiotic of from 0.1:1 to 4:1. A composition as claimed in Claim 1, wherein said amino acid is a compound of general formula II: H₂N-X-COOH (II) wherein X represents a C₁-C₁₀ alkylene group or a C₁-C₁₀ alkylene group having at least one substituent selected from hydroxy groups, C₁-C₄ alkoxy groups, C₆-C₁₄ aryloxy groups, substituted C₆-C₁₄ aryloxy groups, C₇-C₉ aralkyloxy groups, substituted C₇-C₉ aralkyloxy groups, mercapto groups, C₁-c₄ alkylthio groups, C₆-C₁₄ arylthio groups, substituted C₆-C₁₄ arylthio groups, C₇-C₉ aralkylthio groups, substituted C₇-C₉ aralkylthio groups, C₂-C₅ carboxyalkylthio groups, amino groups, amino groups having one or two substituents selected from C₁-C₄ alkyl groups, C₆-C₁₄ aryl groups, substituted C₆-C₁₄ aryl groups, C₇-C₉ aralkyl groups, substituted C₇-C₉ aralkyl groups and carboxylic acyl groups, C₆-C₁₄ aryl groups, substituted C₆-C₁₄ aryl groups, carboxy groups, amidino groups, sulpho groups, C₁-C₄ alkylsulphinyl groups, C₁-C₄ alkylsulphonyl groups and heterocyclic groups having from 5 to 14 ring atoms of which from 1 to 5 are nitrogen and/or oxygen and/or sulphur hetero-atoms, said substituted aryloxy, arylthio, aralkylthio, aryl and aralkyl groups having at least one substituent selected from C₁-C₄ alkyl groups, hydroxy groups amino groups and C₁-C₄ alkoxy groups, or a pharmaceutically acceptable salt thereof. A composition as claimed in Claim 2, wherein X represents a C₁-C₅ alkylene group which is unsubstituted or has one or two substituents selected from: hydroxy groups; C₁-C₄ alkoxy groups; aryloxy groups wherein the aryl ring has from 6 to 14 ring carbon atoms and which is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; C₇-C₉ aralkyloxy groups, wherein the aryl moiety is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; mercapto groups; C₁-C₄ alkylthio groups; arylthio groups wherein the aryl ring has from 6 to 14 ring carbon atoms and which is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; C₇-C₉ aralkylthio groups wherein the aryl ring is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; carboxyalkylthio groups in which the alkyl part has from 1 to 4 carbon atoms; amino groups; amino groups having one or two C₁-C₄ alkyl substituents; amino groups having one or two aryl substituents in which the aryl ring has from 6 to 14 ring carbon atoms and is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; amino groups having one or two C₇-C₉ aralkyl substituents in which the aryl part is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; amino groups having one or two carboxylic acyl substituents; aryl groups having from 6 to 14 ring carbon atoms and being unsubstituted or having from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; carboxy groups; and heterocyclic groups having from 5 to 9 ring atoms, of which from 1 to 3 are nitrogen and/or oxygen and/or sulphur hetero-atoms. A composition as claimed in Claim 2, wherein X represents a C₁-C₅ alkylene group which is unsubstituted or has 1 or 2 substituents selected from: hydroxy groups; C₁-C₄ alkoxy groups; mercapto groups; C₁-C₄ alkylthio groups; amino groups; amino groups having one or two C₁-C₄ alkyl substituents; amino groups having one or two carboxylic acyl substituents; aryl groups having from 6 to 14 carbon atoms wherein the aryl ring is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; carboxy groups; and heterocyclic groups having from 5 to 9 ring atoms, of which from 1 to 3 are nitrogen and/or oxygen hetero-atoms. A composition as claimed in any one of Claims 1 to 4, wherein the N -acyl group is: a C₁-C₁₈ alkanoyl group; a C₃-C₈ alkenoyl group; a C₃-C₈ alkynoyl group; an aromatic acyl group wherein the aryl part is C₆-C₁₄ carbocyclic aryl and is unsubstituted or has from 1 to 5 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, C₁-C₄ alkoxy groups, amino groups, sulpho groups and halogen atoms; a cycloalkanecarbonyl group where the cycloalkane part is C₃-C₈ and is unsubstituted or has at least one substituent selected from C₁-C₄ alkyl groups and phenyl groups; an araliphatic acyl group in which the aryl ring is a carbocyclic ring having from 6 to 14 carbon atoms and which is unsubstituted or has from 1 to 5 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, C₁-C₄ alkoxy groups, amino groups, sulpho groups and halogen atoms, and in which the alkyl moiety has from 1 to 4 carbon atoms; a heterocyclic acyl group which has a saturated or unsaturated ring system, the rings having 5 or 6 ring atoms, of which from 1 to 3 are nitrogen and/or sulphur and/or oxygen hetero-atoms and the ring being unsubstituted or having from 1 to 3 substituents selected from C₁-C₄ alkyl groups and hydroxy groups; a C₂-C₇ alkoxycarbonyl group; an aralkyloxycarbonyl group where the aralkyl part has from 7 to 9 carbon atoms and is unsubstituted or has from 1 to 5 substituents selected from amino groups, C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups and hydroxy groups; or an acyl group derived from an amino acid by removal of OH from the carboxylic acid group and N -acylation of the amino group with at least one of the above-mentioned acyl groups. A composition as claimed in any one of Claims 1 to 4, wherein the N -acyl group is: a saturated aliphatic acyl group having from 1 to 8 carbon atoms; an aromatic acyl group in which the aryl moiety has from 6 to 10 ring carbon atoms and is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups; an alicyclic acyl group in which the cycloalkane ring has from 3 to 6 carbon atoms; an araliphatic acyl group in which the aryl ring has from 6 to 10 ring carbon atoms and the alkyl group has from 1 to 4 carbon atoms, the aryl ring being unsubstituted or having from 1 to 3 substituents selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups; a heterocyclic acyl group in which the heterocyclic ring is saturated or unsaturated and has 5 or 6 ring atoms of which one is a nitrogen, sulphur or oxygen hetero-atom; an alkoxycarbonyl group having a total of from 2 to 7 carbon atoms; an aralkyloxycarbonyl group in which the aralkyl moiety has from 7 to 9 carbon atoms and the aryl ring is unsubstituted or has from 1 to 3 substituents selected C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups; or an acyl group derived from an amino acid by removal of OH from the carboxylic acid group and N -acylation of the amino group with at least one of the above-mentioned acyl groups. A composition as claimed in any; one of Claims 1 to 4, wherein the N -acyl group is: an aromatic acyl group in which the aryl ring has from 6 to 10 ring atoms and which is unsubstituted or has a single substituent selected from C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups, hydroxy groups and amino groups; an alicyclic acyl group in which the cycloalkane moiety has from 3 to 6 carbon atoms; a phenylaliphatic acyl group in which the phenyl group is unsubstituted or has a single C₁-C₄ alkyl substituent, and in which the alkyl part has from 1 to 4 carbon atoms; an alkoxycarbonyl group having a total of from 4 to 6 carbon atoms; an aralkyloxycarbonyl group in which the aralkyl part has from 7 to 9 carbon atoms and has 0 to 1 substituent selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups; or an acyl group derived from an amino acid by removal of OH from the carboxylic acid group and N -acylation of the amino group with at least one of the above-mentioned acyl groups. A composition as claimed in any one of Claims 1 to 4 wherein the N -acyl group is an acetyl, benzoyl, cyclohexanecarbonyl, cyclopropanecarbonyl, hexanoyl, isobutyryl, crotonoyl, ethoxycarbonyl, 4-hydroxybenzoyl, anisoyl, 4-aminobenzoyl, naphthoyl, toluoyl, benzyloxycarbonyl or 4-methoxybenzyloxycarbonyl group. A composition as claimed in any one of Claims 1 and 5 to 8, wherein said amino acid is glycine, β-alanine, 4-aminobutyric acid, 5-aminovaleric acid, 6-aminohexanoic acid, 8-aminooctanoic acid, alanine, 2-aminobutyric acid, norvaline valine, leucine, isoleucine, norleucine, tyrosine, O -methyltyrosine, aspartic acid, glutamic acid, 4-carboxyglutamic acid, 3-methylaspartic acid, 2-aminoadipic acid, 2-aminopimelic acid, 2-aminosuberic acid, 3-hydroxyaspartic acid, 3-hydroxyglutamic acid, 2,3-diaminopropionic acid, 2,4-diaminobutyric acid, 5-hydroxylysine, arginine, N δ , N δ -dimethylornithine, N ε -methyllysine, cysteine, methionine, ethionine, S -carboxymethylcysteine, S -benzylcysteine, methionine S -oxide, ethionine S -oxide, methionine S , S -dioxide, cysteic acid, serine, O -methylserine, threonine, O -methylthreonine, homothreonine, ethoxinine, 3-methoxyvaline, 3-phenylserine, 3-methyl-3-phenylalanine, histidine, tryptophan, 2-methylalanine, 2-methylserine, 2-hydroxyisoleucine, 2-methylmethionine, 2-ethyl-2-phenylglycine, 3-aminobutyric acid, 3-amino-4-methylvaleric acid, 3-amino-3-phenylpropionic acid, 3-amino-2-hydroxypropionic acid or 4-amino-3-hydroxybutyric acid. A composition as claimed in any one of Claims 1 and 5 to 8, wherein said amino acid is glycine, β-alanine, 4-aminobutyric acid, 5-aminovaleric acid, 6-aminohexanoic acid, 8-aminooctanoic acid, alanine, norvaline, valine, leucine, isoleucine, norleucine, N δ , N δ -dimethylornithine, methionine, ethionine, O -methylserine, O -methylthreonine, ethoxinine, 3-methoxyvaline, 3-phenylserine, 3-methyl-3-phenylalanine, histidine, 2-methylalanine, 2-methylserine, 2-hydroxyisoleucine, 2-ethylphenylglycine, 3-aminobutyric acid, 3-amino-4-methylvaleric acid or 3-amino-3-phenylpropionic acid. A composition as claimed in any one of Claims 1 and 5 to 8, wherein said amino acid is β-alanine, 4-aminobutyric acid, 5-aminovaleric acid, 6-aminohexanoic acid, alanine, valine, leucine, norleucine, methionine, histidine or glycine. A composition as claimed in any one of Claims 1 and 5 to 8, wherein said amino acid is leucylglycine, glycyl-β-alanine, glycylalanine, valylalanine, leucylalanine, glycylvaline, alanylvaline, leucylvaline, valylleucine, phenylalanylleucine, histidylleucine, glycylphenylalanine, alanylphenylalanine, leucylphenylalanine, glycylmethionine, valylmethionine, glycylhistidine, alanylvalylglycine, glycylalanylvaline, glycylphenylalanylleucine or glycylglycylhistidine. A composition as claimed in Claim 1, wherein said N -acylated amino acid is: N -( p -toluoyl)-β-alanine N -(4-methoxybenzoyl)-β-alanine N -(3-hydroxy-2-naphthoyl)-β-alanine N -benzoylglycyl-β-alanine N -benzoyl-β-alanine N -benzoyl-5-aminovaleric acid N -benzoyl-6-aminohexanoic acid N -cyclohexanecarbonyl-6-aminohexanoic acid N -( N -methylnicotinoyl)-6-aminohexanoic acid N -benzoyl-8-aminooctanoic acid N -benzoylalanine N -(1-naphthoyl)alanine N -benzoylvalylalanine N -benzoyl-2-aminobutyric acid N -benzoylnorvaline N -valerylvaline N -benzoylalanylvaline N -benzoylvaline N -benzoylleucine N -benzoylglycylphenylalanylleucine N -benzoylnorleucine N -benzoylglycylphenylalanine N -benzoylalanylphenylalanine N -cyclohexanecarbonylleucylphenylalanine N -benzoyl- O -methyltyrosine N -benzoylmethionine N -phenylacetylmethionine N -benzoylvalylmethionine N -benzoylethionine N -(4-methoxybenzyloxycarbonyl)ethionine N -benzoylthreonine N -benzoylhistidine N -( p -toluoyl)histidine N -(4-methoxybenzoyl)histidine N -(4-methoxybenzoyl)-3-aminobutyric acid or N -butyryl-3-amino-3-phenylpropionic acid. A composition as claimed in any one of the preceding Claims, wherein said antibiotic is a compound of general formula I: in which: Y represents a sulphur atom, a methylene group or a methylene group having 1 or 2 methyl and/or methoxy substituents; and R¹ represents a C₁-C₆ alkyl group, a C₁-C₆ alkyl group having at least one of substituents (i) or a heterocyclic group having from 4 to 14 ring atoms of which from 1 to 5 are nitrogen and/or oxygen and/or sulphur hetero-atoms where said heterocyclic group is unsubstituted or has at least one of substituents (ii); substituents (i): halogen atoms, amino groups, amino groups having at least one of substituents (iii), C₁-C₄ alkylideneamino groups, C₁-C₄ aminoalkylideneamino groups, amidino groups, amidino groups having from 1 to 3 of substituents (iii), heterocyclic groups having from 4 to 14 ring atoms of which from 1 to 5 are nitrogen and/or oxygen and/or sulphur hetero-atoms wherein said heterocyclic group is unsubstituted or has at least one of substituents (ii), imino groups, cyano groups, carbamoyl groups and carbamoyl groups having at least one substituent selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups; substituents (ii): C₁-C₆ alkanimidoyl groups, C₁-C₆ alkyl groups, alkoxyalkyl groups where the alkoxy and alkyl parts are each C₁-C₄, carbamoyl groups, carbamoyl groups having at least one substituent selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups, C₁-C₄ haloalkyl groups, heterocyclic acylimidoyl groups where the heterocyclic part has from 5 to 9 ring atoms of which from 1 to 3 are nitrogen and/or oxygen and/or sulphur hetero-atoms, amidino groups, amidino groups having from 1 to 3 of substituents (iii), imino groups, oxygen atoms, C₁-C₆ alkanoyl groups, C₁-C₆ alkanesulphonyl groups, C₁-C₆ alkanesulphinyl groups, hydroximino groups, C₁-C₄ alkoximino groups, carbamoyloxy groups, carbamoyloxy groups having at least one substituent selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups, carbamoyloxylalkyl groups where the alkyl part is C₁-C₄ and the carbamoyl part is unsubstituted or has at least one substituent selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups and C₁-C₄ iminoalkyl groups; substituents (iii): C₁-C₆ alkyl groups, C₂-C₆ alkenyl groups, C₂-C₆ alkynyl groups, and said alkyl, alkenyl and alkynyl groups having at least one substituent selected from halogen atoms, carbamoyloxy groups and carbamoyloxy groups having at least one substituent selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups; and pharmaceutically acceptable salts thereof. A composition as claimed in Claim 14, wherein Y represents a sulphur atom, a methylene group, or the group CH₃-CH<, CH₃O-CH< or (CH₃)₂C<. A composition as claimed in Claim 14 or Claim 15, wherein R¹ represents an ethyl, 2-fluoroethyl, 2-(aminomethyleneamino)ethyl, N¹ , N¹ -dimethylamidinomethyl, N ¹, N ¹, N ²-trimethylamidinomethyl, 3-pyrrolidinyl, 1-formimidoyl-3-pyrrolidinyl, 1-acetimidoyl-3-pyrrolidinyl, 1-propionimidoyl-3-pyrrolidinyl, 2-methyl-1,4,5,6-tetrahydro-5-pyrimidinyl, 2-methoxymethyl-1,4,5,6-tetrahydro-5-pyrimidinyl, 3-azetidinyl, 1-acetimidoyl-3-azetidinyl, N¹ -methyl- N ¹-(2-propynyl)amidinomethyl, N ¹-(2-fluoroethyl)- N¹ -methylamidinomethyl, N¹ -(3-fluoropropyl)- N¹ -methylamidinomethyl, N¹ -methyl- N¹ -(2,2,2-trifluoroethyl)amidinomethyl,1-(3-azetidinyl)ethyl, 1-(1-acetimidoyl-3-azetidinyl)ethyl, 1,4,5,6-tetrahydro-2-pyrimidinylmethyl, 1-(4,5-dihydro-2-thiazolyl)ethyl, 5-carbamoyl-3-pyrrolidinyl, 1-acetimidoyl-5-carbamoyl-3-pyrrolidinyl, 2-chloromethyl-1,4,5,6-tetrahydro-5-pyrimidinyl, 1-butyrimidoyl-3-pyrrolidinyl, 1-nicotinimidoyl-3-pyrrolidinyl, N ¹, N ¹-diallylamidinomethyl, N ¹-methyl- N ¹-(2-propynyl)amidino, N ¹-(2-fluoroethyl)- N ¹-methylamidino, N ¹-(3-fluoropropyl)- N ¹-methylamidino, N ¹-methyl- N ¹-(2,2,2-trifluoroethyl)amidino, N ¹-allyl- N ¹-methylamidinomethyl, cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 2-cyano-1-methylethyl, 2-aminoethyl, 1-carbamoylethyl, 2-(1-aminoethylideneamino)ethyl, 1-amidino-3-pyrrolidinyl, 2-methyl-1,3-diazabicyclo-[3.3.0]oct-2-en-7-yl, 2-methoxymethyl-1,3-diazabicyclo[3.3.0]oct-2-en-7-yl, 5-imino-2-pyrrolidinyl, 2-imino-5-piperidinyl, 1-acetimidoyl-5-methylcarbamoyl-3-pyrrolidinyl, 1-acetimidoyl-5-methoxycarbamoyl-3-pyrrolidinyl, 2-imino-2-( S -oxothiomorpholino)ethyl, 2-imino-2-(1,1-dioxo-1,3-thiazolidin-3-yl)ethyl, 2-imino-2-( S , S -dioxothiomorpholino)ethyl, 2-imino-2-(3,5-dioxo-1-piperazinyl)ethyl, 2-imino-2-(4-methyl-3,5-dioxo-1-piperazinyl)ethyl, 2-imino-2-(-3-oxo-1-piperazinyl)ethyl, 2-imino-2-(4-methyl-3-oxo-1-piperazinyl)ethyl, 2-imino-2-(4-acetyl-3-oxo-1-piperazinyl)ethyl, 2-imino-2-(4-methanesulphonyl-3-oxo-1-piperazinyl)ethyl, N ¹-(2-carbamoyloxyethyl)- N ¹-methylamidinomethyl, 2-(3-hydroximino-1-pyrrolidinyl)2-iminoethyl, 2-imino-2-(3-methoximino-1-pyrrolidinyl)ethyl, 2-(4-hydroximinopiperidino)-2-iminoethyl, 2-imino-2-(4-methoximinopiperidino)ethyl, 2-(3-carbamoyloxy-1-pyrrolidinyl)-2-iminoethyl, 2-imino-2-(3-oxo-1-piperazinyl)ethyl, 2-(3-carbamoylpiperidino)-2-iminoethyl, 2-(3-carbamoyloxypiperidino)-2-iminoethyl, 2-(2-carbamoyloxy-1-pyrrolidinyl)-2-iminoethyl, 2-(2-carbamoyloxymethyl-1-pyrrolidinyl)-2-iminoethyl, 2-(4-carbamoyloxypiperidino)-2-iminoethyl, 2-(4-formyl-1-piperazinyl)-2-iminoethyl, 2-(4-acetyl-1-piperazinyl)-2-iminoethyl, 1-formyl-3-azetidinyl, 1-iminomethyl-3-azetidinyl, 1-methyl-4-piperidyl, 1-acetimidoyl-4-piperidyl or 1-acetyl-3-pyrrolidinyl group. A composition as claimed in Claim 14, wherein said antibiotic is: (5 R ,6 S )-2-{2-[(aminomethylene)amino]ethylthio}-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (5 R ,6 S )-2[(3 S )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (5 R ,6 S )-2-[(3 R )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (5 R ,6 S )-2-[(3 R )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-1( S )-methyl-2-carbapenem-3-carboxylic acid (5 R ,6 S )-2-[(3 S )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-1( R )-methyl-2-carbapenem-3-carboxylic acid (5 R ,6 S )-2-[(3 S )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-1( S )-methyl-2-carbapenem-3-carboxylic acid or (5 R ,6 S )-2-[(3 S )-1-acetimidoyl-5( S )-carbamoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid. A composition as claimed in any one of the preceding Claims, wherein the weight ratio of said N -acylated amino acid to said antibiotic is from 0.1:1 to 4:1. A packaged pharmaceutical preparation comprising: (a) in one part, a penem or carbapenem antibiotic; and (b) in another part, a pharmaceutically acceptable N -acylated derivative of an amino acid wherein the amino group and the carboxylic acid group are attached to a saturated aliphatic carbon chain or carbon atom, or a salt thereof, provided that the amino acid is not ornithine, lysine, phenylalanine or phenylglycine alone. A preparation as claimed in Claim 19, wherein said N -acylated amino acid is as defined in any one of Claims 2 to 13. A preparation as claimed in Claim 19 or Claim 20, wherein said antibiotic is as defined in any one of Claims 14 to 17. The use for the manufacture of a medicament for the treatment of bacterial infections of: (a) a penem or carbapenem antibiotic; in association with: (b) a pharmaceutically acceptable N -acylated derivative of an amino acid wherein the amino group and the carboxylic acid group are attached to a saturated aliphatic carbon chain or carbon atom, or a salt thereof, provided that the amino acid is not ornithine, lysine, phenylalanine or phenylglycine alone. The use as claimed in Claim 22, wherein said N -acylated amino acid is as defined in any one of Claims 2 to 13. The use as claimed in Claim 22 or Claim 23, wherein said antibiotic is as defined in any one of Claims 14 to 17. Claims for the following contracting States : AT, ES A method of making a pharmaceutical composition by mixing: a penem or carbapenem antibiotic; and a pharmaceutically acceptable N -acylated derivative of an amino acid wherein the amino group and the carboxylic acid group are attached to a saturated aliphatic carbon chain or carbon atom, or a salt thereof, provided that, where the composition comprises only one amino acid derivative, the amino acid is not ornithine, lysine, phenylalanine or phenylglycine, the amount of amino acid derivative being sufficient to alleviate any renal toxicity of the antibiotic, preferably in a weight ratio of said N -acylated amino acid to said antibiotic of from 0.1:1 to 4:1. A method as claimed in Claim 1, wherein said amino acid is a compound of general formula II: H₂N-X-COOH (II) wherein X represents a C₁-C₁₀ alkylene group or a C₁-C₁₀ alkylene group having at least one substituent selected from hydroxy groups, C₁-C₄ alkoxy groups, C₆-C₁₄ aryloxy groups, substituted C₆-C₁₄ aryloxy groups, C₇-C₉ aralkyloxy groups, substituted C₇-C₉ aralkyloxy groups, mercapto groups, C₁-C₄ alkylthio groups, C₆-C₁₄ arylthio groups, substituted C₆-C₁₄ arylthio groups, C₇-C₉ aralkylthio groups, substituted C₇-C₉ aralkylthio groups, C₂-C₅ carboxyalkylthio groups, amino groups, amino groups having one or two substituents selected from C₁-C₄ alkyl groups, C₆-C₁₄ aryl groups, substituted C₆-C₁₄ aryl groups, C₇-C₉ aralkyl groups, substituted C₇-C₉ aralkyl groups and carboxylic acyl groups, C₆-C₁₄ aryl groups, substituted C₆-C₁₄ aryl groups, carboxy groups, amidino groups, sulpho groups, C₁-C₄ alkylsulphinyl groups, C₁-C₄ alkylsulphonyl groups and heterocyclic groups having from 5 to 14 ring atoms of which from 1 to 5 are nitrogen and/or oxygen and/or sulphur hetero-atoms, said substituted aryloxy, aralkyloxy, arylthio, aralkylthio, aryl and aralkyl groups having at least one substituent selected from C₁-C₄ alkyl groups, hydroxy; groups, amino groups and C₁-C₄ alkoxy groups, or a pharmaceutically acceptable salt thereof. A method as claimed in Claim 2, wherein X represents a C₁-C₅ alkylene group which is unsubstituted or has one or two substituents selected from: hydroxy groups; C₁-C₄ alkoxy groups; aryloxy groups wherein the aryl ring has from 6 to 14 ring carbon atoms and which is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; C₇-C₉ aralkyloxy groups, wherein the aryl moiety is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; mercapto groups; C₁-C₄ alkylthio groups; arylthio groups wherein the aryl ring has from 6 to 14 ring carbon atoms and which is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; C₇-C₉ aralkylthio groups wherein the aryl ring is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; carboxyalkylthio groups in which the alkyl part has from 1 to 4 carbon atoms; amino groups; amino groups having one or two C₁-C₄ alkyl substituents; amino groups having one or two aryl substituents in which the aryl ring has from 6 to 14 ring carbon atoms and is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; amino groups having one or two C₇-C₉ aralkyl substituents in which the aryl part is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; amino groups having one or two carboxylic acyl substituents; aryl groups having from 6 to 14 ring carbon atoms and being unsubstituted or having from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; carboxy groups; and heterocyclic groups having from 5 to 9 ring atoms, of which from 1 to 3 are nitrogen and/or oxygen and/or sulphur hetero-atoms. A method as claimed in Claim 2, wherein X represents a C₁-C₅ alkylene group which is unsubstituted or has 1 or 2 substituents selected from: hydroxy groups; C₁-C₄ alkoxy groups; mercapto groups; C₁-C₄ alkylthio groups; amino groups; amino groups having one or two C₁-C₄ alkyl substituents; amino groups having one or two carboxylic acyl substituents; aryl groups having from 6 to 14 carbon atoms wherein the aryl ring is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, amino groups and C₁-C₄ alkoxy groups; carboxy groups; and heterocyclic groups having from 5 to 9 ring atoms, of which from 1 to 3 are nitrogen and/or oxygen hetero-atoms. A method as claimed in any one of Claims 1 to 4, wherein the N -acyl group is: a C₁-C₁₈ alkanoyl group; a C₃-C₈ alkenoyl group; a C₃-C₈ alkynoyl group; an aromatic acyl group wherein the aryl part is C₆-C₁₄ carbocyclic aryl and is unsubstituted or has from 1 to 5 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, C₁-C₄ alkoxy groups, amino groups, sulpho groups and halogen atoms; a cycloalkanecarbonyl group where the cycloalkane part is C₃-C₈ and is unsubstituted or has at least one substituent selected from C₁-C₄ alkyl groups and phenyl groups; an araliphatic acyl group in which the aryl ring is a carbocyclic ring having from 6 to 14 carbon atoms and which is unsubstituted or has from 1 to 5 substituents selected from C₁-C₄ alkyl groups, hydroxy groups, C₁-C₄ alkoxy groups, amino groups, sulpho groups and halogen atoms, and in which the alkyl moiety has from 1 to 4 carbon atoms; a heterocyclic acyl group which has a saturated or unsaturated ring system, the rings having 5 or 6 ring atoms, of which from 1 to 3 are nitrogen and/or sulphur and/or oxygen hetero-atoms and the ring being unsubstituted or having from 1 to 3 substituents selected from C₁-C₄ alkyl groups and hydroxy groups; a C₂-C₇ alkoxycarbonyl groups; an aralkyloxycarbonyl group where the aralkyl part has from 7 to 9 carbon atoms and is unsubstituted or has from 1 to 5 substituents selected from amino groups, C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups and hydroxy groups; or an acyl group derived from an amino acid by removal of OH from the carboxylic acid group and N -acylation of the amino group with at least one of the above-mentioned acyl groups. A method as claimed in any one of Claims 1 to 4, wherein the N -acyl group is: a saturated aliphatic acyl group having from 1 to 8 carbon atoms; an aromatic acyl group in which the aryl moiety has from 6 to 10 ring carbon atoms and is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups; an alicyclic acyl group in which the cycloalkane ring has from 3 to 6 carbon atoms; an araliphatic acyl group in which the aryl ring has from 6 to 10 ring carbon atoms and the alkyl group has from 1 to 4 carbon atoms, the aryl ring being unsubstituted or having from 1 to 3 substituents selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups; a heterocyclic acyl group in which the heterocyclic ring is saturated or unsaturated and has 5 or 6 ring atoms of which one is a nitrogen, sulphur or oxygen hetero-atom; an alkoxycarbonyl group having a total of from 2 to 7 carbon atoms; an aralkyloxycarbonyl group in which the aralkyl moiety has from 7 to 9 carbon atoms and the aryl ring is unsubstituted or has from 1 to 3 substituents selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups; or an acyl group derived from an amino acid by removal of OH from the carboxylic acid group and N -acylation of the amino group with at least one of the above-mentioned acyl groups. A method as claimed in any one of Claims 1 to 4, wherein the N -acyl group is: an aromatic acyl group in which the aryl ring has from 6 to 10 ring atoms and which is unsubstituted or has a single substituent selected from C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups, hydroxy groups and amino groups; an alicyclic acyl group in which the cycloalkane moiety has from 3 to 6 carbon atoms; a phenylaliphatic acyl group in which the phenyl group is unsubstituted or has a single C₁-C₄ alkyl substituent, and in which the alkyl part has from 1 to 4 carbon atoms; an alkoxycarbonyl group having a total of from 4 to 6 carbon atoms; an aralkyloxycarbonyl group in which the aralkyl part has from 7 to 9 carbon atoms and has 0 or 1 substituent selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups; or an acyl group derived from am amino acid by removal of OH from the carboxylic acid group and N -acylation of the amino group with at least one of the above-mentioned acyl groups. A method as claimed in any one of Claims 1 to 4, wherein the N -acyl group is an acetyl, benzoyl, cyclohexanecarbonyl, cyclopropanecarbonyl, hexanoyl, isobutyryl, crotonoyl ethoxycarbonyl, 4-hydroxybenzoyl, anisoyl, 4-aminobenzoyl, naphthoyl, toluoyl, benzyloxycarbonyl or 4-methoxybenzyloxycarbonyl group. A method as claimed in any one of Claims 1 and 5 to 8, wherein said amino acid is glycine, β-alanine, 4-aminobutyric acid, 5-aminovaleric acid, 6-aminohexanoic acid, 8-aminooctanoic acid, alanine, 2-aminobutyric acid, norvaline, valine, leucine, isoleucine, norleucine, tyrosine, O -methyltyrosine, aspartic acid, glutamic acid, 4-carboxyglutamic acid, 3-methylaspartic acid, 2-aminoadipic acid, 2-aminopimelic acid, 2-aminosuberic acid, 3-hydroxyaspartic acid, 3-hydroxyglutamic acid, 2,3-diaminopropionic acid 2,4-diaminobutyric acid, 5-hydroxylysine, arginine, N δ , N δ -dimethylornithine, N ε -methyllysine, cysteine, methionine, ethionine, S -carboxymethylcysteine, S -benzylcysteine, methionine S -oxide, ethionine S -oxide, methionine S , S -dioxide, cysteic acid, serine, O -methylserine, threonine, O -methylthreonine, homothreonine, ethoxinine, 3-methoxyvaline, 3-phenylserine, 3-methyl-3-phenylalanine, histidine, tryptophan, 2-methylalanine, 2-methylserine 2-hydroxyisoleucine, 2-methylmethionine, 2-ethyl-2-phenylglycine, 3-aminobutyric acid, 3-amino-4-methylvaleric acid, 3-amino-3-phenylpropionic acid, 3-amino-2-hydroxypropionic acid or 4-amino-3-hydroxybutyric acid. A method as claimed in any one of Claims 1 and 5 to 8, wherein said amino acid is glycine, β-alanine, 4-aminobutyric acid, 5-aminovaleric acid, 6-aminohexanoic acid, 8-aminooctanoic acid, alanine, norvaline, valine, leucine, isoleucine, norleucine, N δ , N δ -dimethylornithine, methionine, ethionine, O -methylserine, O -methylthreonine, ethoxinine, 3-methoxyvaline, 3-phenylserine, 3-methyl-3-phenylalanine, histidine, 2-methylalanine, 2-methylserine, 2-hydroxyisoleucine, 2-ethylphenylglycine, 3-aminobutyric acid, 3-amino-4-methylvaleric acid or 3-amino-3-phenylpropionic acid. A method as claimed in any one of Claims 1 and 5 to 8, wherein said amino acid is β-alanine, 4-aminobutyric acid, 5-aminovaleric acid, 6-aminohexanoic acid, alanine valine leucine, norleucine methionine, histidine or glycine. A method as claimed in any one of Claims 1 and 5 to 8, wherein said amino acid is leucylglycine, glycyl-β-alanine, glycylalanine, valylalanine, leucylalanine, glycylvaline, alanylvaline, leucylvaline, valylleucine phenylalanylleucine, histidylleucine, glycylphenylalanine, alanylphenylalanine, leucylphenylalanine, glycylmethionine valylmethionine, glycylhistidine, alanylvalylglycine, glycylalanylvaline, glycylphenylalanylleucine or glycylglycylhistidine. A method as claimed in Claim 1, wherein said N -acylated amino acid is: N -( p -toluoyl)-β-alanine N -(4-methoxybenzoyl)-β-alanine N -(3-hydroxy-2-naphthoyl)-β-alanine N -benzoylglycyl-β-alanine N -benzoyl-β-alanine N -benzoyl-5-aminovaleric acid N -benzoyl-6-aminohexanoic acid N -cyclohexanecarbonyl-6-aminohexanoic acid N -( N -methylnicotinoyl)-6-aminohexanoic acid N -benzoyl-8-aminooctanoic acid N -benzoylalanine N -(1-naphthoyl)alanine N -benzoylvalylalanine N -benzoyl-2-aminobutyric acid N -benzoylnorvaline N -valerylvaline N -benzoylalanylvaline N -benzoylvaline N -benzoylleucine N -benzoylglycylphenylalanylleucine N -benzoylnorleucine N -benzoylglycylphenylalanine N -benzoylalanylphenylalanine N -cyclohexanecarbonylleucylphenylalanine N -benzoyl- O -methyltyrosine N -benzoylmethionine N -phenylacetylmethionine N -benzoylvalylmethionine N -benzoylethionine N -(4-methoxybenzyloxycarbonyl)ethionine N -benzoylthreonine N -benzoylhistidine N -( p -toluoyl)histidine N -(4-methoxybenzoyl)histidine N -(4-methoxybenzoyl)-3-aminobutyric acid or N -butyryl-3-amino-3-phenylpropionic acid. A method as claimed in any one of the preceding Claims, wherein said antibiotic is a compound of general formula I: in which: Y represents a sulphur atom, a methylene group or a methylene group having 1 or 2 methyl and/or methoxy substituents; and R¹ represents a C₁-C₆ alkyl group, a C₁-C₆ alkyl group having at least one of substituents (i) or a heterocyclic group having from 4 to 14 ring atoms of which from 1 to 5 are nitrogen and/or oxygen and/or sulphur hetero-atoms where said heterocyclic group is unsubstituted or has at least one of substituents (ii); substituents (i): halogen atoms, amino groups, amino groups having at least one of substituents (iii), C₁-C₄ alkylideneamino groups, C₁-C₄ aminoalkylideneamino groups, amidino groups, amidino groups having from 1 to 3 of substituents (iii), heterocyclic groups having from 4 to 14 ring atoms of which from 1 to 5 are nitrogen and/or oxygen and/or sulphur hetero-atoms wherein said heterocyclic group is unsubstituted or has at least one of substituents (ii), imino groups, cyano groups, carbamoyl groups and carbamoyl groups having at least one substituent selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups; substituents (ii): C₁-C₆ alkanimidoyl groups, C₁-C₆ alkyl groups, alkoxyalkyl groups where the alkoxy and alkyl parts are each C₁-C₄, carbamoyl groups, carbamoyl groups having at least one substituent selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups, C₁-C₄ haloalkyl groups, heterocyclic acylimidoyl groups where the heterocyclic part has from 5 to 9 ring atoms of which from 1 to 3 are nitrogen and/or oxygen and/or sulphur hetero-atoms, amidino groups, amidino groups having from 1 to 3 of substituents (iii), amino groups, oxygen atoms, C₁-C₆ alkanoyl groups, C₁-C₆ alkanesulphonyl groups, C₁-C₆ alkanesulphinyl groups, hydroximino groups, C₁-C₄ alkoximino groups, carbamoyloxy groups, carbamoyloxy groups having at least one substituent selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups, carbamoyloxyalkyl groups where the alkyl part is C₁-C₄ and the carbamoyl part is unsubstituted or has at least one substituent selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups and C₁-C₄ iminoalkyl groups; substituents (iii): C₁-C₆ alkyl groups, C₂-C₆ alkenyl groups, C₂-C₆ alkynyl groups, and said alkyl, alkenyl and alkynyl groups having at least one substituent selected from halogen atoms, carbamoyloxy groups and carbamoyloxy groups having at least one substituent selected from C₁-C₄ alkyl groups and C₁-C₄ alkoxy groups; and pharmaceutically acceptable salts thereof. A method as claimed in Claim 14, wherein Y represents a sulphur atom, a methylene group, or the group CH₃-CH<, CH₃O-CH< or (CH₃)₂C<. A method as claimed in Claim 14 or Claim 15, wherein R¹ represents an ethyl, 2-fluoroethyl, 2-(aminomethyleneamino)ethyl, N¹ , N¹ -dimethylamidinomethyl, N¹ , N¹ , N² -trimethylamidinomethyl, 3-pyrrolidinyl, 1-formimidoyl-3-pyrrolidinyl, 1-acetimidoyl-3-pyrrolidinyl, 1-propionimidoyl-3-pyrrolidinyl, 2-methyl-1,4,5,6-tetrahydro-5-pyrimidinyl, 2-methoxymethyl-1,4,5,6-tetrahydro-5-pyrimidinyl, 3-azetidinyl, 1-acetimidoyl-3-azetidinyl, N¹ -methyl- N¹ -(2-propynyl)amidinomethyl, N¹ -(2-fluoroethyl)- N ¹-methylamidinomethyl, N¹ -(3-fluoropropyl)- N¹ -methylamidinomethyl, N¹ -methyl- N¹ -(2,2,2-trifluoroethyl)amidinomethyl, 1-(3-azetidinyl)ethyl, 1-(1-acetimidoyl-3-azetidinyl)ethyl, 1,4,5,6-tetrahydro-2-pyrimidinylmethyl, 1-(4,5-dihydro-2-thiazolyl)ethyl, 5-carbamoyl-3-pyrrolidinyl, 1-acetimidoyl-5-carbamoyl-3-pyrrolidinyl, 2-chloromethyl-1,4,5,6-tetrahydro-5-pyrimidinyl, 1-butyrimidoyl-3-pyrrolidinyl, 1-nicotinimidoyl-3-pyrrolidinyl, N ¹-, N ¹-diallylamidinomethyl, N ¹-methyl- N ¹-(2-propynyl)amidino, N ¹-(2-fluoroethyl)- N ¹-methylamidino, N ¹-(3-fluoropropyl)- N ¹-methylamidino, N ¹-methyl- N ¹-(2,2,2-trifluoroethyl)amidino, N ¹-allyl- N ¹-methylamidinomethyl, cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 2-cyano-1-methylethyl, 2-aminoethyl, 1-carbamoylethyl, 2-(1-aminoethylideneamino)ethyl, 1-amidino-3-pyrrolidinyl, 2-methyl-1-3-diazabicyclo-[3.3.0]oct-2-en-7-yl, 2-methoxymethyl-1,3-diazabicyclo[3.3.0]oct-2-en-7-yl, 5-imino-2-pyrrolidinyl, 2-imino-5-piperidinyl, 1-acetimidoyl-5-methylcarbamoyl-3-pyrrolidinyl, 1-acetimidoyl-5-methoxycarbamoyl-3-pyrrolidinyl, 2-imino-2-( S -oxothiomorpholino)ethyl, 2-imino-2-(1,1-dioxo-1,3-thiazolidin-3-yl)ethyl, 2-imino-2-( S , S -dioxothiomorpholino)ethyl, 2-imino-2-(3,5-dioxo-1-piperazinyl)ethyl, 2-imino-2-(4-methyl-3,5-dioxo-1-piperazinyl)ethyl, 2-imino-2-(3-oxo-1-piperazinyl)ethyl, 2-imino-2-(4-methyl-3-oxo-1-piperazinyl)ethyl, 2-imino-2-(4-acetyl-3-oxo-1-piperazinyl)ethyl, 2-imino-2-(4-methanesulphonyl-3-oxo-1-piperazinyl)ethyl, N ¹-(2-carbamoyloxyethyl) N ¹-methylamidinomethyl, 2-(3-hydroximino-1-pyrrolidinyl)-2-iminoethyl, 2-imino-2-(3-methoximino-1-pyrrolidinyl)ethyl, 2-(4-hydroximinopiperidino)-2-iminoethyl, 2-imino-2-(4-methoximinopiperidino)ethyl, 2-(3-carbamoyloxy-1-pyrrolidinyl)-2-iminoethyl, 2-imino-2-(3-oxo-1-piperazinyl)ethyl, 2-(3-carbamoylpiperidino)-2-iminoethyl, 2-(3-carbamoyloxypiperidino)-2-iminoethyl, 2-(2-carbamoyloxy-1-pyrrolidinyl)-2-iminoethyl, 2-(2-carbamoyloxymethyl-1-pyrrolidinyl)-2-iminoethyl, 2-(4-carbamoyloxypiperidino)-2-iminoethyl, 2-(4-formyl-1-piperazinyl)-2-iminoethyl, 2-(4-acetyl-1-piperazinyl)-2-iminoethyl, 1-formyl-3-azetidinyl, 1-iminomethyl-3-azetidinyl, 1-methyl-4-piperidyl, 1-acetimidoyl-4-piperidyl or 1-acetyl-3-pyrrolidinyl group. A method as claimed in Claim 14, wherein said antibiotic is: (5 R ,6 S )-2-{2-[(aminomethylene)amino]ethylthio}-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (5 R ,6 S )-2-[(3 S -1-acetimidoylpyrrolidin-3-ylthio]-6-[1 R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (5 R ,6 S )-2-[(3 R )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (5 R ,6 S )-2-[(3 R )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-1( S )-methyl-2-carbapenem-3-carboxylic acid (5 R ,6 S )-2-[(3 S )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-1( R )-methyl-2-carbapenem-3-carboxylic acid (5 R ,6 S -2-[(3 S )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R -hydroxyethyl]-1( S )-methyl-2-carbapenem-3-carboxylic acid or (5 R ,6 S )-2-[(3 S )-1-acetimidoyl-5( S )-carbamoylpyrrolidin-3-ylthio]-6-[1( R -hydroxyethyl]-2-carbapenem-3-carboxylic acid. A method as claimed in any one of the preceding Claims, wherein the weight ratio of said N -acylated amino acid to said antibiotic is from 1:1 to 4:1. A method according to any one of the preceding Claims, which comprises: solubilizing said N -acylated amino acid in water; adding and dissolving said antibiotic in the resulting; and optionally lyophilizing the solution to provide a powdery mixture. A method according to Claim 19, in which said N -acylated amino acid is solubilized by dispersing it in water and adding sufficient of a base to adjust the pH to a value of from 5.5 to 9. The use for the manufacture of a medicament for the treatment of bacterial infections of: (a) a penem or carbapenem antibiotic; in association with: (b) a pharmaceutically acceptable N -acylated derivative of an amino acid wherein the amino group and the carboxylic acid group are attached to a saturated aliphatic carbon chain or carbon atom, or a salt thereof, provided that the amino acid is not ornithine, lysine, phenylalanine or phenylglycine alone. The use as claimed in Claim 21, wherein said N -acylated amino acid is: N -( p -toluoyl)-β-alanine N -(4-methoxybenzoyl)-β-alanine N -(3-hydroxy-2-naphthoyl)-β-alanine N -benzoylglycyl-β-alanine N -benzoyl-β-alanine N -benzoyl-5-aminovaleric acid N -benzoyl-6-aminohexanoic acid N -cyclohexanecarbonyl-6-aminohexanoic acid N -( N -methylnicotinoyl)-6-aminohexanoic acid N -benzoyl-8-aminooctanoic acid N -benzoylalanine N -(1-naphthoyl)alanine N -benzoylvalylalanine N -benzoyl-2-aminobutyric acid N -benzoylnorvaline N -valerylvaline N -benzoylalanylvaline N -benzoylvaline N -benzoylleucine N -benzoylglycylphenylalanylleucine N -benzoylnorleucine N -benzoylglycylphenylalanine N -benzoylalanylphenylalanine N -cyclohexanecarbonylleucylphenylalanine N -benzoyl- O -methyltyrosine N -benzoylmethionine N -phenylacetylmethionine N -benzoylvalylmethionine N -benzoylethionine N -(4-methoxybenzyloxycarbonyl)ethionine N -benzoylthreonine N -benzoylhistidine N -( p -toluoyl)histidine N -(4-methoxybenzoyl)histidine N -(4-methoxybenzoyl)-3-aminobutyric acid or N -butyryl-3-amino-3-phenylpropionic acid. The use as claimed in Claim 21 or Claim 22, wherein said antibiotic is: (5 R ,6 S )-2-{2-[(aminomethylene)amino]ethylthio}-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (5 R ,6 S )-2-[(3 S )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (5 R ,6 S )-2-[(3 R )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid (5 R ,6 S )-2-[(3 R )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-1( S )-methyl-2-carbapenem-3-carboxylic acid (5 R ,6 S )-2-[(3 S -1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-1( R )-methyl-2-carbapenem-3-carboxylic acid (5 R ,6 S )-2-[(3 S )-1-acetimidoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-1( S -methyl-2-carbapenem-3-carboxylic acid or (5 R ,6 S )-2-[(3 S )-1-acetimidoyl-5( S )-carbamoylpyrrolidin-3-ylthio]-6-[1( R )-hydroxyethyl]-2-carbapenem-3-carboxylic acid.

Inventors: IWATA, MASAYUKI C/O PRODUCT DEVELOPMENT LABS., KAWAHARA, YUKINORI C/O PRODUCT DEVELOPMENT LABS., SHIOKARI, TAKASHI C/O PRODUCT DEVELOPMENT LABS., UEDA, SEIGO C/O PRODUCT DEVELOPMENT LABS.
Applicants: SANKYO COMPANY LIMITED
Application year: 1986
Main classification: A61K31
IPC codes: A61K31