Abstract:
N-alkylamide of DL and L(-)-carnitine having general formula (I) ##STR1## wherein: x -   is OH -   or the anion of a pharmacologically acceptable acid (preferably Cl -` ), and 
     R is a straight C 10  -C 16  alkyl radical 
     are prepared via transamination by reacting DL or L(-)-carnitinamide halogenide with an amine of formula NH 2  R wherein R has the above-identified meaning in an acid environment (e.g. H 3  PO 4 ) in the presence of a high-boiling solvent (e.g. ethylene glycol). 
     N-alkylamides (I) are endowed with potent antibacterial activity and are suitable for preparing pharmaceutical and cosmetic compositions.

Description:
FIELD OF THE INVENTION 
     The present invention relates to novel N-alkylamides of D,L and L(-)-carnitine endowed with antibacterial activity, having general formula (I) ##STR2## wherein 
     X -  is OH -  or the anion of a pharmacologically acceptable acid, and 
     R is a straight C 10  -C 16  alkyl radical. 
     Preferably, X -  is Cl - . 
     The present invention also relates to a process for producing N-alkylamides of formula (I) and pharmaceutical and cosmetic compositions comprising an amount of at least one of the N-alkylamides (I) suitable for promoting an effective antibacterial action. 
     BACKGROUND OF THE INVENTION 
     Some carnitine N-alkylamildes are known already. 
     In Japanese patent 408435 filed Oct. 31, 1960 in the name of Takeda Chemical Industries, Ltd. carnitinamides structurally analogous to those of formula (I) are disclosed, wherein, however, the radical R is lower alkyl (methyl and ethyl). This Japanese patent discloses that such amides &#34;promote the intestinal peristalsis and are useful as medicaments for intestinal disorders&#34;. These amides are prepared by condensing at room temperature a reactive carnitine derivative (an acid halogenide, ester or anhydride) with methylamine or ethylamine. 
     DETAILED DESCRIPTION 
     The N-alkylamides of D,L and L(-)-carnitine according to the present invention are unlike the amides of Japanese Patent 408435 prepared via a process which comprises the following two characterizing steps: 
     (a) reacting an alkylamine of formula NH 2  R wherein R is a straight C 10  -C 16  alkyl radical with a substantially equimolar amount of H 3  PO 4 , at 120°-140° C., for 2-4 hours, in an atmosphere of an inert gas, in the presence of a high-boiling solvent; and 
     (b) adding to the reaction mixture a mixture of D,L or L(-)-carnitinamide chloride and alkylamine NH 2  R, at a molar ratio of about 1:1.1, the molar amount of D,L or L(-)-carnitinamide chloride being about twice as much the molar amount of H 3  PO 4  and keeping the resulting reaction mixture under stirring at about 110°-130° C. for about 34-38 hours in an atmosphere of inert gas. 
     After removal under vacuum of the high-boiling solvent, the residue comprising the N-alkylamide (I) is purified and the compound isolated according to known procedures. 
     The transamination of this process allows the direct conversion of the amide into the N-alkylamides (I) to be carried out. No intermediate steps are needed in order to convert the starting amide in one of those activated compounds (acid halogenides, esters or anhydrides) from which substituted amides are usually obtained (in this regard see the above mentioned Takeda patent). It is apparent that these intermediate steps would lower the yield remarkably and would increase the cost of the end product. 
     The following non-limiting example illustrates the preparation of one of the N-alkylamides (I) according to the process of this invention. 
    
    
     EXAMPLE 
     Preparation of D,L-N-dodecylcarnitinamide chloride 
     A mixture of dodecylamine (25 m moles), ethylene glycol (20.0 grams) and 85% H (25 m moles) was reacted in a 100-ml round bottom flask, sealed with a rubber stopper, under stirring, at 130° C. for 3 hours under nitrogen. 
     A mixture of D,L-carnitinamide chloride (50 m moles) and dodecylamine (55 m moles) was then added to the reaction mixture. 
     The resulting mixture was kept under stirring at 120° C. for 36 hours under nitrogen. When ammonia development ceased, the reaction mixture was cooled and ethylene glycol caused to evaporate at 80° C. under 0.5 mm Hg. 
     After the residue was dissolved in 80 ml of chloroform, the resulting solution was chromatographed on a silica (50 g) containing column. The product was first eluted with chloroform (100 ml) and with 100 ml of a 9:1 chloroform: isopropanol mixture; then, the product was eluted with 300 ml of a 1:1 chloroform:methanol mixture. The product was recovered by evaporation from the solvent. By further crystallization from 100 ml of tetrahydrofurane and then 100 ml of a 1:1 chloroform:tetrahydrofurane mixture (twice repeated) the title compound was obtained ##EQU1## 
     Elementary analysis: 
     C=62.87%; H=11.50%; N=7.86%; Cl=10.25% O=7.52% . 
     Also the remaining N-alkylamides of D,L and L(-)-carnitine chloride encompassed in the general formula (I) were prepared by the same process. In the following table, the main chemico-physical characteristics of the compounds are listed. 
     
         __________________________________________________________________________ ##STR3##                                IR spectraAbbreviated      Molecular  Elementary Analysis                                Freq.R   name   weight            [α].sub.D.sup.25                 Theoretical (%)                         Found (%)(*)                                cm.sup.-1                                      Assignments__________________________________________________________________________C.sub.10 H.sub.21    L(-) CA-10      336.92            -13.62°                 C = 60.60                         C = 60.72                                 950  OH    DL-CA-10     0°                 H = 10.77                         H = 10.54                                1300  CN                 N = 8.31                         N = 8.85                                1470  CH.sub.2 and OH                 Cl = 10.52                         Cl = 10.00                                1560  NH                 O = 9.50                         O = 8.89                                1650                                       ##STR4##C.sub.11 H.sub.23    L(-) CA-11      350.97            -13.05°                 C = 61.60                         C = 61.93                                2940  OH    DL-CA-11     0°                 H = 10.91                         H = 11.29                                3300  OH                 N = 7.98                         N = 8.05                                The frequencies and the                 Cl = 10.10                         Cl = 9.80                                corresponding assignments                 O = 9.12                         O = 8.84                                can be regarded as identicalC.sub.12 H.sub.25    L(-) CA-12      364.97            -12.60°                 C = 62.53                         C = 62.87                                for all the compounds    DL-CA-12     0°                 H = 11.05                         H = 11.50                                because the differences                 N = 7.68                         N = 7.86                                between them are not                 Cl = 9.71                         Cl = 10.25                                significant.                 O = 8.77                         O = 7.52C.sub.13 H.sub.27    L(-) CA-13      379.03            -12.23°                 C = 63.34                         C = 63.65    DL-CA-13     0°                 H = 11.17                         H = 10.81                 N = 7.39                         N = 7.60                 Cl = 9.35                         Cl =  9.02                 O = 8.44                         O = 8.92C.sub.14 H.sub.29    L(-) CA-14      393.03            -12.01°                 C = 64.18                         C = 64.94    DL-CA-14     0°                 H = 11.28                         H = 12.00                 N = 7.13                         N = 7.19                 Cl = 9.02                         Cl = 9.87                 O = 6.14                         O = 6.00C.sub.15 H.sub.31    L(-) CA-15      407.08            -11.62°                 C = 64.91                         C = 64.99    DL-CA-15     0°                 H = 11.39                         H = 10.92                 N = 6.88                         N = 6.89                 Cl = 8.71                         Cl = 8.69                 O = 7.86                         O = 8.51C.sub.16 H.sub.33    L(-) CA-16      421.08            -11.08                 C = 65.61                         C = 64.98    DL-CA-16     0°                 H = 11.49                         H = 11.87                 N = 6.65                         N = 6.64                 Cl =  8.42                         Cl = 8.97                 O = 7.60                         O = 7.54__________________________________________________________________________ (*) For both L(-) and DL form the &#34;found&#34; values are substantially identical 
    
     TOXICOLOGICAL TESTS 
     1. Acute toxicity 
     (1.1) Acute toxicity via the oral route in mice 
     It was evaluated in albino Swiss mice weighing 20-25 g which had been kept fasting 12 hours before administration. 
     The compounds dissolved in distilled water were administrated to the animals by gavage. 
     The animals were divided in groups of 6 animals each and treated with solutions of diminishing concentrations, each concentration being one half of the preceding concentration. 
     The mice were checked for 7 days following administration in order to verify their possible death or any behavioural alteration. 
     LD 50  was evaluated by the Carrol Weil method (Biometrics, Sept. 1952, pages 249-255, &#34;Calculation of median-effective dose&#34;). 
     The results thus obtained are illustrated in table 1 and 1A. 
     
                       TABLE 1______________________________________Acute Toxicity via the oral route in miceDL-CA-10      DL-CA-12  DL-CA-14   DL-CA-16______________________________________LD.sub.50   791       1512      1125     1995(mg/kg)Dose(mg/kg)4000    --        6/6       6/6      6/62000    6/6       5/6       6/6      3/61000    3/6       0/6       2/6      0/6 500    0/6       0/6       0/6      0/6 250    0/6       --        --       --______________________________________ 
    
     
                       TABLE 1A______________________________________Acute Toxicity via the oral route in miceL(-)-CA-10    L(-)-CA-12                   L(-)-CA-14 L(-)-CA-16______________________________________LD.sub.50   890       1256      1125     1995(mg/kg)Dose(mg/kg)4000    --        6/6       6/6      6/62000    6/6       6/6       6/6      2/61000    4/6       1/6       2/6      1/6 500    0/6       0/6       0/6      0/6 250    0/6       --        --       --______________________________________ 
    
     (1.2) Acute toxicity via the intravenous route in mice 
     It was evaluated in albino Swiss mice weighing 20-25 g. 
     The animals were injected the compounds dissolved in saline solution, in their caudal vein. 
     The animals were divided in groups of 6 animals each and treated with solutions of diminishing concentration, each concentration being one half of the preceding concentration. The mice were checked for 48 hours following administration. 
     LD 50  was evaluated by the Carrol Weil method. 
     The results are illustrated in table 2 and 2A. 
     
                       TABLE 2______________________________________Acute Toxicity via the intravenous route in miceDL-CA-10      DL-CA-12  DL-CA-14   DL-CA-16______________________________________LD.sub.50   28.28     25.2      48.72    63.33(mg/kg)Dose(mg/kg)160     --        --        6/6      6/680      6/6       6/6       6/6      6/640      5/6       6/6       3/6      2/620      1/6       1/6       0/6      0/610      0/6       0/6       --       --______________________________________ 
    
     
                       TABLE 2A______________________________________Acute Toxicity via the intravenous route in miceL(-)-CA-10    L(-)-CA-12                   L(-)-CA-14 L(-)-CA-16______________________________________LD.sub.50   28.28     25.2      63.33    56.42(mg/kg)Dose(mg/kg)160     --        --        6/6      6/680      6/6       6/6       6/6      6/640      5/6       6/6       2/6      0/620      1/6       1/6       0/6      0/610      0/6       0/6       --       --______________________________________ 
    
     (1.3) Assessment of the irritating activity on the rabbit eye 
     The Federal Register test (vol. 38, 1973) modified as hereinbelow indicated was used. 
     Six New Zealand albino rabbits, weighing 1.5-2 kgs, were used for each test substance. Throughout the test the animals were caged so as to exclude possible extraneous materials that may produce eye irritation. 
     0.1 ml of a 1% solution of the test compounds was instilled with a dropper into the conjunctival sac of the rabbit right eye (the contralateral eye remained untreated and served as a control), whereupon the animals were caged again. 
     The treated eyes of all the animals were examined, in comparison with the control eye, 24, 48 and, if necessary, 72 hours following treatment. 
     The irritating activity was rated based on the scoring scale outlined in table 3. 
     The results are illustrated in table 4 and 4A. 
     
                       TABLE 3______________________________________Assessment of irritating activity on rabbit eyes______________________________________Conjunctivae(a)   Conjestion Vessels normal            0 Vessels slightly injected 1 Diffuse redness, vessels definetly injected                           2 not easily discernible Diffuse, beefy red        3(b)   Chemosis No oedema                 0 Slight oedema             1 Severe oedema with eversion of lids                           2 Severe oedema with lids about half closed                           3 Severe oedema with lids more than half closed                           4CorneaNo alteration or opacity    0Scattered or confluent areas of opacity;                       1details of iris visibleEasily discernible translucent areas; details                       2of iris slightly obscuredNacreous area; no details of iris visible;                       3contours of pupil barely discernibleComplete corneal opacity; iris not discernible                       4IrisNormal                      0Markedly deepened folds, more numerous than                       1normal; congestion, swelling, moderate circum-corneal injection; iris still reacting to lightNo reaction to light; haemorrhage; gross                       2destruction______________________________________ 
    
     
                       TABLE 4______________________________________Assessment of irritation activity on rabbit eyes    DL-CA-10  DL-CA-12  DL-CA-14                                DL-CA-16    irritation              irritation                        irritation                                irritationRABBIT No.    score     score     score   score______________________________________1        2         2         4       22        2         4         4       43        0         2         0       44        0         2         0       25        2         2         2       66        2         2         2       2Average  1.3       2.3       2.0     3.3score______________________________________ 
    
     
                       TABLE 4A______________________________________Assessment of irritaiton activity on rabbit eyes    L(-)-CA-10              L(-)-CA-12                        L(-)-CA-14                                L(-)-CA-16    irritation              irritation                        irritation                                irritationRABBIT No.    score     score     score   score______________________________________1        2         2         2       62        0         2         4       43        2         4         0       04        2         0         0       25        2         2         2       46        0         4         2       2Average  1.3       2.3       1.5     3score______________________________________ 
    
     (1.4) Assessment of the cutaneous irritation activity in rabbits 
     Irritation to the skin was evaluated by the method illustrated in Federal Register (vol. 38, No. 187, page 27019, 1973) on albino rabbits weighing about 2 kgs. 
     Two days before the test was commenced, the back of the rabbits was clipped free of hair with an electric shearing machine, taking care not to bring about irritations and abrasions. 
     At test beginning, a zone of the skin was abraded by a sterile syringe needle. 
     Both on the intact and abraded skin an AL-test patch soaked in a 20% solution of the test compound was secured in place. 
     Similar patches (controls) soaked in the same volume of saline solution were secured in place on the intact and abraded skin. 
     The AL-test patches were secured in place to the animals by antiallergic adhesive plasters 
     After 24 hours of exposures the patches were removed and the skin examined. 
     The reactions were evaluated at 24 and 72 hours on the basis of the table in Federal Register (see table 5). The results thus obtained are illustrated in table 6 and 6A. 
     
                       TABLE 5______________________________________Assessment of the cutaneous irritating activitySKIN REACTIONS:______________________________________(1)   ERYTHEMA No erythema                0 Slight barely perceptible erythema                            1 Well-defined erythema      2 Moderate to severe erythema                            3 Severe erythema (intense redness)                            4 to slight eschar formation(2)   OEDEMA No oedema                  0 Slight, barely perceptible oedema                            1 Slight oedema (with well-defined edges)                            2 Moderate oedema (raised approximately 1 mm)                            3 Severe oedema (raised more than 1 mm and                            4 extending beyond the exposure area)______________________________________ 
    
     The reaction value is the average of the values of six animals and is calculated by adding the values under 1) to the values under 2) for both intact and abraded skin. The resulting sum is divided by 24 and the result is termed &#34;primary cutaneous irritation score&#34;. 
     The substance is regarded as: 
     non-irritating if the score is 0 
     mildly irritating if the score ranges between 0 and 2 
     averagely irritating if the score ranges between 2 and 5 
     severely irritating if the score ranges between 5 and 8 
     
                                           TABLE 6__________________________________________________________________________Assessment of the cutaneous irritating activity__________________________________________________________________________    DL-CA-10 (*)              DL-CA-12 (**)    Erythema value after               Oedema value after                              Erythema value after                                         Oedema value afterRabbit    Skin 24 hours         72 hours               24 hours                    72 hours                         Total                              24 hours                                   72 hours                                         24 hours                                              72 hours                                                     Total__________________________________________________________________________ 1   intact     0    0     0    0    0    0    0     2    0                                                     4    abraded    0    0     0    0    0    0    0     2    0 2   intact     0    0     0    0    0    0    0     2    0                                                     4    abraded    0    0     0    0    0    0    0     2    0 3   intact     0    0     0    0    0    0    0     2    0                                                     4    abraded    0    0     0    0    0    0    0     2    0 4   intact     0    0     0    0    0    0    0     2    0                                                     4    abraded    0    0     0    0    0    0    0     2    0 5   intact     0    0     0    0    0    0    0     2    0                                                     4    abraded    0    0     0    0    0    0    0     2    0 6   intact     0    0     0    0    0    0    0     2    0                                                     4    abraded    0    0     0    0    0    0    0     2    0irritation score    0                         1__________________________________________________________________________    DL-CA-14 (**)             DL-CA-16 (*)    Erythema value after               Oedema value after                              Erythema value after                                         Oedema value afterRabbit    Skin 24 hours         72 hours               24 hours                    72 hours                         Total                              24 hours                                   72 hours                                         24 hours                                              72 hours                                                     Total__________________________________________________________________________ 1   intact     0    0     0    0    0    0    0     0    0      0    abraded    0    0     0    0    0    0    0     0    0      0 2   intact     0    0     0    0    0    0    0     0    0      0    abraded    0    0     0    0    0    0    0     0    0      0 3   intact     0    0     0    0    0    0    0     0    0      0    abraded    0    0     0    0    0    0    0     0    0      0 4   intact     0    0     0    0    0    0    0     0    0      0    abraded    0    0     0    0    0    0    0     0    0      0 5   intact     0    0     0    0    0    0    0     0    0      0    abraded    0    0      0   0    0    0    0     0    0      0 6   intact     0    0     0    0    0    0    0     0    0      0    abraded    0    0     0    0    0    0    0     0    0      0irritation score    0                         0__________________________________________________________________________ (*) Exposure period: 4 hours (**) Exposure period: 24 hours 
    
     
                                           TABLE 6A__________________________________________________________________________Assessment of the cutaneous irritating activity__________________________________________________________________________    L(-)-CA-10 (*)            L(-)-CA-12 (**)    Erythema value after               Oedema value after                              Erythema value after                                         Oedema value afterRabbit    Skin 24 hours         72 hours               24 hours                    72 hours                         Total                              24 hours                                   72 hours                                         24 hours                                              72 hours                                                     Total__________________________________________________________________________ 1   intact     0    0     0    0    0    0    0     2    0                                                     4    abraded    0    0     0    0    0    0    0     2    0 2   intact     0    0     0    0    0    0    0     2    0                                                     4    abraded    0    0     0    0    0    0    0     2    0 3   intact     0    0     0    0    0    0    0     2    0                                                     4    abraded    0    0     0    0    0    0    0     2    0 4   intact     0    0     0    0    0    0    0     2    0                                                     4    abraded    0    0     0    0    0    0    0     2    0 5   intact     0    0     0    0    0    0    0     2    0                                                     4    abraded    0    0     0    0    0    0    0     2    0 6   intact     0    0     0    0    0    0    0     2    0                                                     4    abraded    0    0     0    0    0    0    0     2    0irritation score    0                         1__________________________________________________________________________    L(-)-CA-14 (**)           L(-)-CA-16 (*)    Erythema value after               Oedema value after                              Erythema value after                                         Oedema value afterRabbit    Skin 24 hours         72 hours               24 hours                    72 hours                         Total                              24 hours                                   72 hours                                         24 hours                                              72 hours                                                     Total__________________________________________________________________________ 1   intact     0    0     0    0    0    0    0     0    0      0    abraded    0    0     0    0    0    0    0     0    0      0 2   intact     0    0     0    0    0    0    0     0    0      0    abraded    0    0     0    0    0    0    0     0    0      0 3   intact     0    0     0    0    0    0    0     0    0      0    abraded    0    0     0    0    0    0    0     0    0      0 4   intact     0    0     0    0    0    0    0     0    0      0    abraded    0    0     0    0    0    0    0     0    0      0 5   intact     0    0     0    0    0    0    0     0    0      0    abraded    0    0      0   0    0    0    0     0    0      0 6   intact     0    0     0    0    0    0    0     0    0      0    abraded    0    0     0    0    0    0    0     0    0      0irritation score    0                         0__________________________________________________________________________ (*) Exposure period: 4 hours (**) Exposure period: 24 hours 
    
     ANTIBACTERIAL ACTIVITY 
     in vitro 
     1.1 Determination of antibacterial activity on Petri plates 
     The test was carried out on sterile Petri plates (14 cm of diameter), by inoculating the strains listed at point A in suitable culture media by the Kirby-Bauer method. A) 
     1 - Bacillus subtilis ATCC 6633 on Muller Hinton agar 
     2 - Escherichia coli ATCC 25922 on Muller Hinton agar 
     3 - Staphylococcus aureus ATCC 6538 on Muller Hinton agar 
     4 - Mucor mucedo ATCC 7941 on Sabouraud maltose agar 
     5 - Candida albicans ATCC 2091 on Sabouraud maltose agar 
     The antibacterial activity of the compounds was evaluated by means of a well on the solidified medium. The results are shown in table 7 and 7A. 
     
                       TABLE 7______________________________________Antibacterial Activity (diameter in mm)Con-                                       Mucorcentra- (DL)               Staph.                          Bac.  Cand. mucedotion  Compound   E. coli aureus                          subtilis                                albic.                                      (*)______________________________________0,1%  C10        10.7    10.8  14.0  12.7  +- C12        19.1    16.9  18.0  17.3  ++ C14        10.6    10.3  10.9  13.4  +- C16        10.4    10.6   9.9  13.5  + 1%   C10        14.1    14.6  27.1  24.0  ++ C12        28.6    19.8  23.0  24.8   +++ C14        12.7    13.0  12.4  16.8  +- C16        11.0    12.4  11.0  14.7  +10%   C12        30.6    21.8  27.0  25.0   +++ C14        15.4    18.1  17.0  17.9  +- C16        11.4    16.1  14.6  16.0  + DL-carnitina-            --      --    --    --    -- mide-chloride______________________________________(*) +- =   10.0 to 12.0 mm in diameter+ =     12.0 to 19.0 mm in diameter++ =    19.0 to 29.0 mm in diameter+++ =   29.0 to 35.0 mm in diameter 
    
     
                       TABLE 7A______________________________________Antibacterial Activity (diameter in mm)Con-                                       Mucorcentra- (DL)               Staph.                          Bac.  Cand. mucedotion  Compound   E. coli aureus                          subtilis                                albic.                                      (*)______________________________________0,1%  C10        10.8    11.5  13.0  12.3  +- C12        20.7    15.6  19.0  18.2  ++ C14        10.6    11.4  10.1  13.8  +- C16        10.9    10.6   9.6  12.0  + 1%   C10        14.8    15.3  24.1  21.0  ++ C12        28.8    18.8  26.0  23.9   +++ C14        11.0    14.1  12.9  16.1  + C16        10.6    13.2  11.5  13.0  +10%   C12        30.6    20.5  27.9  24.8   +++ C14        16.3    19.6  18.1  19.3  + C16        11.5    15.9  13.6  16.4  + DL-carnitina-            --      --    --    --    -- mide-chloride______________________________________(*) +- =   10.0 to 12.0 mm in diameter+ =     12.0 to 19.0 mm in diameter++ =    19.0 to 29.0 mm in diameter+++ =   29.0 to 35.0 mm in diameter 
    
     in vitro 
     2.1 Determination of Minimum Inhibiting Concentration (MIC) 
     The test was carried out on sterile Petri dishes (10 cm of diameter) loaded with 10 ml of medium and anti-bacterial substance at given concentration, mixed at 9:1 ratio. 
     The medium used was 
     (1) Muller Hinton agar for bacteria, and 
     (2) Sabouraud Dextrose agar for fungi 
     The solidified plates were then inoculated at the surface thereof with a multi-point inoculator equipped with 48 rods, each of which had been coated with a suspension of the tested microorganism. The suspensions were prepared with the Kirby-Bauer method (Bauer, Kirby, Sherris, Turck 1966, Am. J. Clin. Pathol. 45:49-496) modified according to D&#39;Amato-Hochstein (D&#39;Amato-Hochstein, 1982, J. Clin. Microb. 15 (2) 282-285). 
     The inoculated plates were incubated at 35° C. (culture medium (1)) and 25° C. (culture medium (2)) respectively. 
     Reading was carried out after 15-18 hours for bacteria and after 24-30 hours for fungi. 
     MIC values thus obtained are shown in table 8 and 8A. 
     
                                           TABLE 8__________________________________________________________________________Minimum Inhibiting Concentration (mcg)Method: Petri dishes with solid culture medium             DL-CA-10                   DL-CA-12                         DL-CA-14                               DL-CA-16__________________________________________________________________________Staphylococcus aureus       10547 62    15    15    15 &#34;          8530  62    31    15    15 &#34;          6538P 31    62    250   &gt;500 &#34;          80R   62    15    15    15 &#34;          58R   62    62    31    31Enterococcus       1 Renz.             62    7     &lt;7    &lt;7 &#34;          2 Renz.             62    7     &lt;7    &lt;7Strept. faecalis lactis R       8043  62    &lt;7    &lt;15   &lt;7 &#34;          66/48 62    7     &lt;7    &lt;7Strept. faecium       UM    31    &lt;7    &lt;7    &lt;7Sarcina lutea       9341  250   62    62    15Bacillus subtilis       6633  62    15    15    31Pseudomonas aeruginosa       3E    &gt;500  250   &gt;500  &gt;500 &#34;          50F   &gt;500  250   &gt;500  &gt;500 &#34;          12F   &gt;500  125   &gt;500  &gt;500Salmonella typhi       SK    125   62    250   &gt;500Salmonella typhi       6539  62    31    15    31Enterobacter cloacae       P99 β -Latt.             250   31    125   &gt;500Shigella somnei       SK    125   62    200   &gt;500Escherichia coli       4     125   62    250   &gt;500 &#34;          828   500   125   &gt;500  &gt;500 &#34;          92F   250   62    250   &gt;500 &#34;          66/46 125   62    &gt;500  &gt;500 &#34;          R57B  250   125   &gt;500  500Klebsiella pneumoniae       IB 1 (pat.)             500   31    250   500Candida albicans       A 215 250   62    15    125 &#34;          i6    250   62    15    62 &#34;          ISS 562             250   62    15    62Candida tropicalis       ISS 5705             250   &lt;7    31    7Mucor mucedo       7941  250   15    15    62Aspergillus niger       9642  500   15    15    15__________________________________________________________________________ 
    
     
                                           TABLE 8A__________________________________________________________________________Minimum Inhibiting Concentration (mcg)Method: Petri dishes with solid culture medium             L(-)-CA-10                   L(-)-CA-12                         L(-)-CA-14                               L(-)-CA-16__________________________________________________________________________Staphylococcus aureus       10547 31    15    15    15 &#34;          8530  31    31    62    15 &#34;          6538P 62    62    250   &gt;500 &#34;          80R   62    15    15    15 &#34;          58R   62    15    15    15Enterococcus       1 Renz.             62    7     15    &lt;7 &#34;          2 Renz.             62    7     &lt;7    &lt;7Strept. faecalis lactis R       8043  62    &lt;7    &lt;7    15 &#34;          66/48 62    7     &lt;7    &lt;7Strept. faecium       UM    31    &lt;7    &lt;7    &lt;7Sarcina lutea       9341  125   62    62    31Bacillus subtilis       6633  125   15    15    31Pseudomonas aeruginosa       3E    &gt;500  250   &gt;500  &gt;500 &#34;          50F   &gt;500  62    &gt;500  &gt;500 &#34;          12F   &gt;500  125   &gt;500  &gt;500Salmonella typhi       SK    125   62    250   250Salmonella typhi       6539  62    31    15    31Enterobacter cloacae       P99 β-Latt.             125   62    125   &gt;500Shigella somnei       SK    125   62    200   &gt;500Escherichia coli       4     125   62    250   &gt;500 &#34;          828   250   125   &gt;500  &gt;500 &#34;          92F   500   62    500   &gt;500 &#34;          66/46 125   125   &gt;500  &gt;500 &#34;          R57B  500   250   &gt;500  &gt;500Klebsiella pneumoniae       IB 1 (pat.)             500   62    250   &gt;500Candida albicans       A 215 250   62    15    125 &#34;          i6    250   62    15    62 &#34;          ISS 562             250   31    31    31Candida tropicalis       ISS 5705             250   &lt;7    31    15Mucor mucedo       7941  250   15    15    62Aspergillus niger       9642  500   15    31    15__________________________________________________________________________ 
    
     ANTIDANDRUFF ACTIVITY 
     in vitro 
     3. DL and L(-) activity on Pityrosporum ovalis ATCC 12078 
     The test was carried out on sterile Petri plates having 10 cm of diameter filled with 10 ml of medium inoculated with the tested microorganism. 
     Sabouraud maltose agar+1% Tween 80 was used as culture medium. 
     The Kirby-Bauer method modified according to D&#39;Amato-Hochstein was used. 
     The plates after inoculation by means of wells on the agar-containing medium were incubated at 35° C. for 48 hours. 
     The diameter of the growth inhibition zone was 20.3 mm for the 1% DL solution and 20.5 mm for the 1% L(-) solution and 9.91 mm for the 0.1% DL solution and 10.2 for the 0.1% L(-) solution. 
     3.2 Minimum inhibiting concentration of DL and L(-) CA-12 on Pityrosporum ovalis ATCC 12078 
     The test was carried out following the method outlined at point 2.1, except that the medium was modified by the addition of 1% Tween 80. The resulting MIC was 50 mcg for both DL and L(-). 
     The compounds of the invention are suitable for being compounded into pharmaceutical, cosmetic and over-the-counter (OTC) compositions, such as mouthwashes, external disinfectants, deodorants, shaving creams and the like. It was found that, generally, the optimum concentration of N-alkylamides of formula (I) in the compositions is 0.1-0.3% by weight for a preservative action and 0.3-1% by weight for a disinfectant action. 
     Some compositions according to the invention are hereinbelow indicated. 
     
         ______________________________________Alcoholic deodorantEthanol               42 gPerfume               0.1 gDL or L(-) CA-12      0.1 gPropylene glycol      3 gSoftigen 767          0.5 gDeionized water       balance to 100 gAlcohol-free deodorantEthanol               3 gSolulan C 24          1 gPerfume               0.1 gPropylene glycol      3 gDL or L(-) CA-12      0.1 gLanidrol (lanolin alcohol)                 0.5 gDeionized water       balance to 100 gShaving creamEsso wax 5250         6 gMarcol 52             6.5 gLaurex CS             10 gTween 60              3 gSilicone oil AK 350   1 gButylhydroxyanisole   0.05 gSteinamid P256        1.7 gDL or L(-) CA-12      0.15 gEDTA                  0.2 g(ethylenediaminetetraacetic acid)Propylene glycol      3 gEmpigen BT            5 gPolimer JR 400        0.1 gPerfume               0.35 gDeionized water       balance to 100 gLiquid detergentEmpilan 2574          1 gTween 20              2.4 gTween 80              1.5 gEmpigen BT            40 gZetesol 250           7.6 gNeo extrapon lemon    0.1 gSigma antioxidant     0.1 gEDTA                  0.1 gDL or L(-) CA-12      0.15 gSolulan 16            0.6 gPhosphoric acid       0.12 gCoconut oil diethanolamide                 3 gDeionized water       balance to 100 gChewing gumChlorofil             0.0027 gSodium fluoride       0.0152 gDL or L(-) CA-12      0.667 gMicronized sorbitol   35.78 gMicronized mannitol   13.55 gGum base              28.74 gAroma                 0.282 gMenthol               0.406 g70% sorbitol solution 17.35 g______________________________________