WO2001066097A2

WO2001066097A2 - Active substance directed against microbes of the genus pseudomonas

Info

Publication number: WO2001066097A2
Application number: PCT/EP2001/002435
Authority: WO
Inventors: Martina Herrmann; Holger Joppe; Gerhard Schmaus
Original assignee: Dragoco Gerberding & Co. Ag
Priority date: 2000-03-07
Filing date: 2001-03-03
Publication date: 2001-09-13
Also published as: AU4418701A; DE10010512A1; WO2001066097A3

Abstract

The invention relates to the use of hydroxychavicol as an antimicrobial active substance directed against microbes of the genus Pseudomonas, especially against Pseudomonas aeruginosa. The minimal inhibitory concentration (MIC) value of hydroxychavicol directed against Pseudomonas aeruginosa is surprisingly low and, to be precise, is a value of 34 ppm. Hydroxychavicol can thus be excellently used for disinfecting and/or for preserving technical, cosmetic or pharmaceutical articles. The invention also relates to the action of hydroxychavicol with regard to other test microbes.

Description

Active ingredient against germs of the genus Pseudomonas

The present invention relates to a highly effective antimicrobial active substance against germs of the genus Pseudomonas, in particular against Pseudomonas aeruginosa.

Pseudomonas aeruginosa (formerly: Pseudomonas pyocyanea) is an aquatic bacterium that can affect humans and can, for example, cause middle ear widening, wound infections and even bacteria in weakened people. A number of antimicrobial agents against Pseudomonas aeruginosa are already known. Nevertheless, there continues to be a need for substances which are effective in low concentrations against Pseudomonas aeruginosa and which are well tolerated by humans and / or the environment.

Surprisingly, it has now been shown that the known compound hydroxychavicol (3,4-dihydroxyallylbenzene; CAS No.: 1126-61-0) is an antimicrobial active ingredient against germs of the genus Pseudomonas, especially Pseudomonas aeruginosa, which is highly effective even in small concentrations. The structural formula of hydroxychavicol is shown below:

Hydroxychavicol is a component of water-based products from PiDer be ^¬ te lB

In a publication on the Anti icrobial Activity of Vaπous Solvent Extracts o ~ Betel Ouid Ingredients. ang et al, Food Science (October, 1997) 24 (5) 49 ^"τ -505, describes the antimicrobial effectiveness of various Piper όeteJ fruit extracts and betel nut extracts. An antimicrobial effect of certain extracts against Streptococcus sa li vanus, Strepto _^ occus sangu is, Ne iεseπa sp .. Sa lmone l la sp., Yers ima enteroco lit ica and L isteria monocvtogenes, although the antimicrobial effect varies between strong and weak, ang et al suspect that in the Phenolic compounds such as eugenol and hydroxychavicol containing extracts are responsible for the antimicrobial activity, but they have not investigated whether the extracts have an activity against Pseudomonas aeruginosa or other germs of the genus Pseudomonas, and also an investigation of the antimicrobial activity of the phenolic substances mentioned in Yang et al have not carried out any separate form.

Yu et a l come in Natl. Be. Counc. Monthly, Roc, 11 (5), 385-394, 1983, to the conclusion that water extracts of Piper betel oil have no antimicrobial activity against a number of microorganisms including Pseudomonas fluorescens.

Finally, Evans et al in a study on 'Identification of Fungicidal and Nematocidal Components in the Leaves of Piper bet le (Piperaceae)', J. Agπc. Food Chem. 1984, 32, 1254-1256, Hydroxychavicol (= Allylpyrocatechol ⁾ and four other allylphenols in Piper £ ete7 chloroform extracts are identified and consider it to be true that some of the biological effects of Piper pray / leaves and - oils can be attributed to the (five in total) identified substances. However, there was no study of the effect of Piper pray 7 extracts on germs of the genus Pseudomonas.

As the structural formula shows, hydroxychavicol is a phenylpropane deπvate. In particular, there is a structurally close relationship to substances such as 3-methoxy.4-hydroxyalylbenzene (= eugenol),

3,4-dimethoxyal lyIbenzene (= eugenol methyl ether. Chavibetolmethyl ether) and 3-hydroxy, 4-methoxyallylbenzene (= Chavibetol), all of which are known as (further) constituents of piper pray / leaves, surprisingly it has been shown that mentioned, structurally closely related to hydroxychavicol against Pseudomonas aeruginosa are significantly less effective than hydroxychavicol itself.

A number of other tπ-substituted benzene derivatives (phenylpropanes), whose MIC values (MIC • = minimal inhibitory concentration) are known from the literature, remain significantly behind hydroxychavicol in their antimicrobial activity against Pseudomonas aeruginosa, sometimes by several orders of magnitude. A comparative overview of the antimicrobial activity of phenylpropane derivatives against Pseudomonas aeruginosa is given in Table 1.

The respective methods for determining the MIC values of the comparison substances compared to Pseudomonas aeruginosa can be found in the literature references given, the method for determining the MIC value for hydroxychavicol results from the examples given below.

Hydroxychavicol has changed under the terms of the usual toxicity and contract! safety tests proven to be good to very good by contract; it can therefore also be used in concentrations well above the MIC for Pseudomonas aeruginosa. In this way, the effect now investigated against other germs can be used if necessary (mi). For more preferred concentration ranges, see below.

Hydroxychavicol as an antimicrobial agent against Pseudomonas aeruginosa can be used in particular for the disinfection and / or preservation of a technical, cosmetic or pharmaceutical article. In this case, the hydroxychavicol is typically allowed to act on an article surface which is already infested or susceptible to infestation or if the composition of the article allows it, it mixes with the article itself.

The term technical article is to be understood in the broadest sense. It includes, for example, food and cleaning agents, textile fabrics, semi-finished plastic products, molded metallic or plastic products, sterile medical articles such as wound dressings and other everyday objects.

In the 'cosmetics' it may be in particular kos ^¬ metic solutions, creams, lotions, gels, sprays, etc. nandeln.

Finally, the 'pharmaceutical articles' can in particular be tablets, capsules, powders or drops to be administered orally, drugs to be administered intravenously, intraocularly, intraperitoneally or intramuscularly, drugs to be applied topically in the form of solutions, creams, lotions, Act gels, sprays or in the form of dressings impregnated with drugs.

The growth of the germ Pseudomonas aeruginosa is inhibited by treating it with an antimicrobial! effective amount of hydroxychavicol treated.

In process (a) for inhibiting the growth of Pseudomonas aeruginosa in or on a technical, cosmetic or pharmaceutical article or (b) for antimicrobial treatment of such an article against Pseudomonas aeruginosa, the respective article (for example the surface thereof) becomes effective with an anti-microbial Treated amount of hydroxychavicol. An antimicrobial! Equipped article is an article that is impregnated with hydroxychavicol or otherwise contacted, so that an attack on the treated article areas with Pseudomonas aeruginosa is completely prevented or at least made more difficult.

The technical, cosmetic or pharmaceutical articles will often be formulations (liquids, creams, pastes and the like) which are mixed with such an amount of hydroxychavicol that their concentration in the treated (mixed with hydroxychavicol) formulation is between 0.1 0034 and 20% by weight (0.0034 % By weight corresponds approximately to the mimmal inhibitory concentration of hydroxychavicol compared to Pseudomonas aeruginosa), preferably between 0.05 and 5% by weight.

If a technical, cosmetic or pharmaceutical formulation contains an amount of hydroxychavicol which is effective against Pseudomonas aeruginosa antimicrobial 1, it is not necessary to provide other substances which are effective against Pseudomonas aeruginosa antimicrobial 1 in the formulation. The presence of other antimicrobial 1 active substances may, for example, be desirable in order to selectively inhibit the growth of other germs. In such cases, it is advantageous to use Hydroxychavicol and one or more other antimicrobials! use effective substances so that the anti-microbial substances complement each other through their (selective) activity against different germs.

Technical, cosmetic or pharmaceutical formulations are therefore advantageous which comprise an amount of hydroxychavicol which is antimicrobially active against Pseudomonas aeruginosa and one or more further antimicrobially active substances, the formulation at least comprising at least one formulation which does not comprise a hydroxychavicol with an otherwise identical composition antimicrobial activity against Pseudomonas aeruginosa increased by a factor of 4. It is preferred if the effect is increased by at least a factor of 8, better by a factor of 16, even better by a factor of 32 or even by a factor of 64. In some cases it is preferred if the antimicrobial effect of the formulation against Pseudomonas aeruginosa is based at least essentially on the presence of hydroxychavicol; this is the case if the effect increases at least by a factor of 128 in comparison with a formulation which does not comprise any hydroxychavicol with an otherwise identical composition

If a formulation comprises, in addition to hydroxychavicol, one or more further (preferably selectively against other germs) antimicrobially active substances, these should advantageously be present in such an amount or concentration that the formulation has antimicrobial activity against individual or all (test) germs from the group is the Corynebacterium xerosis, Escherichia co li, Propiombacteriu acnes, Staphylococcus aureus, Staphy lococcus ep idermidis, Candida a lbicans, Ma lasse∑ ia furfur, Aspergillus niger, Epider ophyton flocossum, Trichophyton mentagrophytes and Trichophyton rubrum. The effect of such a formulation against individual or all (test) germs of the above group in comparison with a formulation which, with an otherwise identical composition, does not comprise any hydroxychavicol should be increased by a maximum of 1.25, preferably by a maximum of 1.10 his. The Hydroxychavicol concentration in the formulation is therefore preferably so limited that a good antimicrobial action against Pseudomonas aeruginosa is ensured by the presence of the Hydroxychavicol, but the other or the other antimicrobial substances are responsible for combating the other germs mentioned. If the effects on Pseudomonas aeruginosa given in the previous paragraph are observed, a formulation is thus available in which (a) hydroxychavicol and (b) the other antimicrobial substance (s) act selectively against different germs.

A large number of anti-microbial active substances with particularly high activity against the other germs mentioned (and nevertheless good tolerance) are known. Using simple experiments, suitable combinations of active substances can be determined in which hydroxychavicol has a predominant activity against germs of the genus Pseudomonas and the second active substance has a predominant effect against another (test) germ.

The concentration of hydroxychavicol in a technical, cosmetic or pharmaceutical formulation, for example a formulation which also comprises other antimicrobial substances, is advantageously between 0.001 and 20% by weight, preferably between 0.05 and 5% by weight.

Hydroxychavicol is synthetically accessible in several ways. For example according to EP 748849 or US 5,792,825 by reacting catechol with allyl chloride, but alternatively also by demethylating eugenol according to the process described in Example 1.

The invention is explained in more detail below with the aid of examples: 1. Synthesis of hydroxychavicol:

Example 1: Synthesis of Hydroxychav ico l

Eugenol (2.58g, 15.75mmol) and Bortπbrormd-Dimethylsulfid-Ko plex (10.0g, 31.5mmol) are refluxed in 1, 2-Dιchlorethan (50ml) under argonate osmare 45min. After cooling, water (35 ml) is added and stirring is continued for 20 min. The mixture is then diluted with diethyl ether (150 ml) and the phases are separated. The organic phase is washed once with saturated sodium bicarbonate solution. The product is then transferred from the organic to the aqueous phase by extraction twice with 1N sodium hydroxide solution (50 ml). The aqueous phase is acidified with 4N hydrochloric acid and extracted twice with diethyl ether (100 ml). After drying the organic phase over magnesium sulfate, filtering off and spinning in a vacuum, the crude product is obtained, which is purified by column chromatography and preparative HPLC (yield: 1.4 g; purity:> 99%).

The structural proof for the substance thus synthesized was carried out by MS, ¹ H and ¹³ C NMR spectroscopy

Spectroscopic data: ¹ H (CDC1 ₃ , 300 MHz): δ (ppm) = 3.18 (d; 6.6 Hz), 4.98 (dd, 9.5, 1.5 Hz) 5.00 (dd, 17.6, 1.5 Hz); 5.84 (tdd, 6.6, 9.5, 17.6 Hz), 6.56 (dd, 1.9.8.1 Hz), 6.65 (d, 1.9 Hz), 6.74 (d, 8.1 Hz); ¹³ C (CDC1 ₃ ; 75.5 MHz): δ (ppm) = 39.4 (t), 115.6 (t), 115.8 (d), 116.1 (d), 121.3 (d), 133.6 (s), 137.5 (d), 141.4 (s), 143.2 (s); MS: m / z (%) = 150 (100, M +).

2. Studies on the antimicrobial action of hydroxychavicol:

The finding that hydroxychavicol is particularly suitable for controlling (inhibiting the growth) of Pseudomonas aeruginosa goes back to a series of tests in which a large number of other test germs were examined in addition to Pseudomonas aeruginosa. In the following, not only the results for the inhibition of Pseudomonas aeruginosa by means of hydroxychavicol are given, but also the results of the further tests. The activity of hydroxychavicol against some of the others Test rhymes are also surprisingly high when compared to other phenolproDan derivatives, especially the activity against Candida a lb icans.

2.1. General test conditions:

The detection of the antimicrobial effect of the hydroxychavicol synthesized according to Example 1 was carried out with the aid of the agar solution method based on DIN 58 940 / ICS and DIN 58 944 / ICS. Petn dishes of 5.5 cm in diameter with 8.7 ml of freshly prepared Muei ler-Hinton agar ( ^' Merck, An. 1.05437 or Wilkins-Chalgren-Agar-Boi Hon, Oxoid, Art CM 643, supplemented with 10 g agar / liter), to which the various concentrations of a respective diluted sample in 3.3% by volume - 0.3 ml were added. Muel ler-Hinton agar containing 3% TweenδO (Merck, Art. 8.22 187) was used for the test germ Ma lassez ia furfur.

2.6 ml of the 3.3% samples were diluted with ethanol (96%; Merck, Art. 1.00971). The further test concentrations of the respective dilution series, which were created in the form of geometric series, were produced by continuous 2: 1 dilution with ethanol (96% -ιg).

A further dilution with the test agar (0.3 ml sample or corresponding dilutions + 8.7 ml agar) resulted in 30-fold lower final concentrations (this corresponds to an initial concentration of 1100 ppm each). The concentrations given below refer to the pure substance and are converted into ppm. 2 agar plates were poured per test concentration and nan medium.

The following controls were carried out with 2 agar plates each:

K1: 9.0 ml Muel ler-Hinton agar (Mueller-H. agar) (unvaccinated)

K2: 8.7 ml Muel ler-Hinton agar + 0.3 ml ethanol (96%) (uninoculated)

K3: 8.7 ml Muel ler Hmton agar + 0.3 ml ethanol (96%) (inoculated;

K4: 9.0 ml Muel ler-Hinton agar (inoculated)

K5: 9.0 ml Mueller H. agar + 3% Tween80 (unvaccinated)

K6: 9.0 ml Mueller H. agar + 3% TweenδO + 0.3 ml ethanol (96%) (unvaccinated)

K7: 9.0 ml Mueller H. agar + 3% TweenSO - 0.3 ml ethanol (96%) (inoculated) K8: 9.0 ml Mueller H. agar + 3% TweenδO (inoculated)

K9: 9.0 ml Wi Ikins-Chalgren agar (uninoculated)

K10 9.0 ml Wilkins-Chalgren agar + 0.3 ml ethanol (96%) (uninoculated ⁾ K11 9.0 ml Wilkins-Chalgren agar + 0.3 ml ethanol ⁽ 96%) (inoculated) K12 9.0 ml Wi Ikins-Chalgren agar (inoculated)

After solidification and drying (approx. 1 h at 37 ° C.), the test plates were inoculated punctually with 1 μl each of the test germ suspensions listed in the examples below. To check purity and identity, the aerobically growing bacteria (Corynebacterium xeros s, Escheπch ia co li, Pseudomonas aeruginosa; Staphylococcus aureus; Staphy lococcus epidermidis) were used on Columbia blood agar (BioMeπeux, Art. 43049), the yeasts (with Except for Ma lassez ia furfur), skin and mold (Candida a lbicans; Aspergi l lus mger; Epidermophyton flocco-su; Trichophyton rubrum; Trichophyton mentagrophytes) cultivated on Sabouraud agar (BioMeπeux, Art. 43555). Ma lassez ia furfur was grown on Sabourad agar with deflowers (TweenδO: 1%, lecithin: 0.3%; histidine: 0.1%; Merck, Art. 1.18368). Propiombacterium acnes was cultivated on Schaedler agar (BioMέrieux, Art. 43273). Further information on the test germs can be found in Table 2.

Table 2: Test germs (strain names) and bacterial counts

Test germ number CFU * / ml

1 Corynebacterium xeros is ATCC 7711 2.2 X 10 ⁷

2 Escheπchia co li ATCC 11229 2.5 X 10 ⁷

3 Propiombacterium acnes ATCC 11829 1.4 X 10 ⁸

4 Pseudomonas aeruginosa ATCC 9027 2.2 X 10 ⁷

5 Staphylococcus aureus ATCC 6538 2.8 X 10 ⁷

6 Staphy lococcus epidermidis ATCC12228 3.1 X 10 ⁷

7 Candida a lbicans ATCC 10231 2.5 X 10 ⁷

8 Ma lassezia furfur DSM 6171 2.0 X 10 ⁷

9 Aspergi 1 lus mger ATCC 16404 2.4 X 10 ⁷

10 Epidermophyton floccosum CBS 55384 2.8 X 10 ⁷

11 Trichophyton mentagrophytes CBS 26379 2.2 x 10 ⁷

1 Trichophyton rubrum DSM 4167 2.0 X 10 ⁷ (* = color-forming units) The test germ suspensions of test germs No. 1, 2 and 4-6 (test germ 4 - Pseudomonas aeruginosa) were prepared by incubating Muel ler-Hinton-Bouil Ion (Merck, Art. 1.10293) at 36 ° C, which with a few individual colonies of the respective test germs had been inoculated. After a clear turbidity had been reached, so much sterile nutrient broth was added to the suspensions that their turbidity corresponded to the McFarland standard 0.5 (approx. 10 ⁸ CFU / ml).

To prepare the remaining test germ suspensions (No. 3 and No. 7-12), the test strains were cultivated on the solid nutrient media mentioned above, harvested using a sterile swab and taken up or diluted in so much Muel ler-Hinton-Boui 1 ion that the turbidity of the suspensions corresponded to the McFarland Standard 0.5.

All test germ suspensions, with the exception of Prop iom ^' bacterium acnes, were again diluted 1:10 with sterile broth and their bacterial count was determined in a surface method using a spiralometer (results: see Table 2).

The inoculated plates were incubated under the conditions given in Table 3 and then evaluated. The lowest active substance concentration at which there is no macroscopic growth was regarded as the MIC (minimal inhibitory concentration). Minimal, barely visible growth or a few small single colonies were rated as inhibitions.

Table 3: Inoculation and incubation

No. Test germ strain reference Growth medium broth conditions

1 Corynebacterium xerosis ATCC 7711 Aerob Mueller-Hinton agar 18h at 36 ° C

2 Escherichia coli ATCC 11229 Aerob Mueller-Hinton agar 18h at 36 ° C

3 Propiombacterium acnes ATCC 11829 Anaerobic Wilkins-Chalgren agar 72h at 36 ° C

4 Pseudomonas aeruginosa ATCC 9027 Aerob Mueller-Hinton agar 18h at 36 ° C

5 Staphylococcus aureus ATCC 6538 Aerob Mueller-Hinton agar 18h at 36 ° C

6 Staphylococcus epidermidis ATCC 12228 Aerob Mueller-Hinton agar 18h at 36 ° C

7 Candida albicans ATCC 10231 Aerob Mueller-Hinton agar for 48 hours at 30 ° C

8 Malassezia furfur DSM 6171 Aerob Mueller-Hinton agar + 72h at 30 ° C

3% Tween 80

9 Aspergillus niger ATCC 16404 Aerob Mueller-Hinton agar for 48 hours at 30 ° C

10 Epidermophyton floccosum CBS 55384 Aerob Mueller-Hinton agar 72h at 30 ° C

11 Trichophyton mentagrophytes CBS 26379 Aerob Mueller-Hinton agar 72h at 30 ° C

12 Trichophyton rubrum DSM 4176 Aerob Mueller-Hinton agar 72h at 30 ° C 2. 2. For example:

The following results for the antimicrobial effect of the Hydrox- ychavicols organisms are also representative for a large number of other Mikroor ^¬ that can be allocated to in Examples 2-5 treated Orgamsmengruppen.

Example 2: Inhibition of the growth of aerobically growing, gram-like germs:

Test microbial suspensions of Corynebacterium xeros is (ATCC 7711), Staphy ^¬ lococcus aureus (ATCC 6538) and Staphylococcus epidermidis (ATCC 12228) were carried out according to the methods described in section 2.1. (General test conditions) inoculated ^¬ be written conditions and incubated. The results are shown in Table 4. A significant inhibition of growth even at a very low concentration was found in Staphylococcus aureus (MNK value: 34 ppm = 34 μg / ml), Staphy lococcus epidermidis (MIC value: 34 ppm = 34 μg / ml) and be i Corynebacterium xeros is ( MIC value of 138 ppm - 138 μg / ml) can be observed.

Table 4: MIC values for Corynebacterium xeros is, Staphylococcus aureus and Staphylococcus epidermidis

Example 3: Inhibition of the growth of aerobically growing, gram-negative seeds

Test microbial suspensions of Escherichia coli (ATCC 11229) and Pseudomonas aeruginosa (ATCC 9027) were prepared according to the procedure described in section 2.1. (General experimental conditions) conditions inoculated and incubated. The results are shown in Table 5. A significant inhibition of wax ^¬ tums already at low concentration could in Escherichia co li (MIC Value: 275 ppm = 275 μg / ml), but particularly in the case of Pseudomonas aeruginosa (MIC value of 34 ppm = 34 μg / ml).

Table 5: MIC values for Escherichia coli (ATCC 11229) and Pseudomonas aerug inosa

Example 4: Inhibition of growth of anaerobically growing, gram-like it ime

A test germ suspension of Propionibacterium acnes (ATCC 11829) was prepared according to the procedure described in section 2.1. (General experimental conditions) conditions inoculated and incubated. The results are shown in Table 6. The MIC value for Propion ibacterium acnes is 1100 ppm = 1100 μg / ml.

Table 6: MIC values for Propion ibacterium acnes (ATCC 11829)

Example 5: Inhibiting the growth of skin and mold patches

Test microbial suspensions from Aspergi lus niger (ATCC 16404), Candida a lbicans (ATCC 10231), Epidermophyton floccosum (CBS 55384), Trichophyton mentagrophytes (CBS 26379), Trichophyton rubrum (DSM 4167), and Ma lassez DSM7urf according to the in section 2.1. (General experimental conditions) conditions inoculated and incubated. The results are shown in Table 7. With all germs an inhibition could of growth can be observed at concentrations below 200 ppm = 200 μg / ml, the MIC value for Candida a lbicans is 34 ppm.

Table 7: MIC values for Candida a lbicans, Ma lassez ia furfur, Aspergi lus niger, Epidermophyton floccosum, Trichophyton mentagrophytes and Trichophyton rubrum

Examples 2-5 describe hydroxychavicol as an antimicrobial substance with a broad spectrum of activity and surprisingly high activity against Pseudomonas aeruginosa and Candida a lbicans. The ^examples show possibilities for the use of hydroxychavicol for the treatment of bacterial, yeast and mold infections. ^¬ application areas are in the pharmaceutical field for the oral or topical treatment of bacterial, Hefen- or fungal infections, especially infections with Pseudomonas aeruginosa.

Hydroxychavicol can also be used in nourishing cosmetic formulations that help maintain the healthy condition of the skin. Special application areas are for example the inhibition of perspiration forming, Doomed for armpit or body odor charge of bacteria (Staphylococcus and Corynebacterium species), the inhibition mycoses ^¬ thing Direction skin and nail fungi (dermatomycosis, onychomycosis, Trichophyton and Ep i de rmophy clay Species), the inhibition of acne-causing microorganisms (Propion ibacterium species) and the inhibition of microorganisms responsible for dandruff formation (Ma lassezia furfur, Syn .; Pityrosporum ova le or P. orbicu lare). Especially preferred is the use of hydroxychavicol to inhibit germs responsible for wound infection (Pseudomonas aeruginosa); the use for the inhibition of yeasts causing candidiasis (eg Candida a lb icans) is also preferred. In both areas of application, surprisingly low concentrations of hydroxychavicol are sufficient to achieve the treatment goal.

Antimicrobial, hydroxychavicol-containing active substance mixtures can be applied both orally (tablets, capsules, powder, drops), intravenously, intraocularly, intraperitoneally, intramuscularly and topically in the form of solutions, creams, lotions, gels, sprays or impregnated dressings.

The concentration of the active ingredient hydroxychavicol in the applied formulations is in the range from 0.001% to 20% and preferably in the range from 0.05% to 5%. The antimicrobial active ingredient complex, in which other antimicrobial active ingredients can also be present in addition to hydroxychavicol (see above), can be used prophylactically or therapeutically. The concentration of an amount of active ingredient to be administered daily, for example, will then depend on the physiological condition of the test subject and on individual-specific parameters such as age or body weight.

As already mentioned several times, hydroxychavicol can be used both alone and in combination with other antimicrobially active substances. This applies in particular to the therapy of diseases, to the use in cosmetic care products and to the use as a preservative.

Table 1: Antimicrobial effects of trisubstituted benzene derivatives (phenyipropanes) against Pseudomonas aeruginosa

Literature:

1. Alexander Pauli; Dissertation; University of Würzburg 1994

2. S.G. Griffim et al; Flavor Frag. J.14, 322-332 (1999)

3. MIC values Dragoco

Claims

claims:

Use of hydroxychavicol as an antimicrobial active substance against germs of the genus Pseudomonas.

Use of hydroxychavicol as an antimicrobial agent against Pseudomonas aerug inosa.

Use according to claim 1 or 2, characterized in that hydroxychavicol is used as an antimicrobial agent for disinfecting and / or preserving a technical, cosmetic or pharmaceutical article.

Use of hydroxychavicol for the manufacture of a pharmaceutical formulation with an antimicrobial activity against Pseudomonas aeruginosa.

Process for inhibiting the growth of Pseudomonas aeruginosa, characterized in that Pseudomonas aeruginosa is treated with an antimicrobially effective amount of hydroxychavicol.

Process (a) for inhibiting the growth of Pseudomonas aeruginosa in or on a technical, cosmetic or pharmaceutical article or (b) for antimicrobial treatment of such an article against Pseudomonas aeruginosa, characterized in that the article is treated with an antimicrobially effective amount of hydroxychavicol approx.

Process according to claim 6, characterized in that the article is a technical, cosmetic or pharmaceutical formulation which is mixed with such an amount of Hvdroxychavicol that its concentration in the treated formulation is between 0.0034 and 20% by weight. is preferably between 0.05 and 5% by weight.

8. Technical, cosmetic or pharmaceutical formulation comprising an amount of hydroxychavicol which is antimicrobially active against Pseudomonas aeruginosa and one or more further antimicrobially active substances, the formulation being at least around that in comparison with a formulation which does not comprise a hydroxychavicol with an otherwise identical composition Factor 4 has increased antimicrobial activity against Pseudomonas aeruginosa.

9. Formulation according to claim 8, characterized in that the concentration of hydroxychavicol in the formulation is between 0.0034 and 20 wt .-%, preferably between 0.05 and 5 wt .-%.

10. Technical, cosmetic or pharmaceutical article which is at least partially equipped with an effective amount of hydroxychavicol against Pseudomonas aeruginosa, the article being better in the equipped area compared to an article which does not comprise hydroxychavicol with an otherwise identical composition, against attack is protected with Pseudomonas aeruginosa or the growth of Pseudomonas aeruginosa.