CA2140920A1

CA2140920A1 - Combination of germicidal agents

Info

Publication number: CA2140920A1
Application number: CA2140920A
Authority: CA
Inventors: Winfried Klein; Eva Matthies; Gerhard Sauermann; Hartmut Schmidt-Lewerkuhne; Robert Schmucker; Bernd Traupe
Original assignee: Individual
Current assignee: Beiersdorf AG
Priority date: 1992-09-05
Filing date: 1993-08-20
Publication date: 1994-03-17
Also published as: DE59308619D1; AU4950993A; AU670966B2; JPH08501091A; ATE166534T1; KR950702796A; JP3529093B2; WO1994005156A1; EP0658082A1; DE4229707A1; ES2118250T3; EP0658082B1

Abstract

Combinations of imidazole and/or one or more derivatives of imidazole which have the following general structural formula - wherein the radicals can have the following meaning:
R1 = H or C(1-25) - alkyl, R2 = H or C(1-25) - alkyl, R3 = H or C(1-25) - alkyl, R4 = H or C(1-25) - alkyl, - wherein R4 can also, and preferably if R1, R2 and R3 are a hydrogen atom, be the radicals and -CH2-CH(NR5R6)-COOR7, wherein R5 = H or C(1-25) - alkyl, R6 = H or C(1-25) - alkyl, R7 = H or C(1-25) - alkyl, and a substance which is active against microorganisms or a mixture from the group of lantibiotics.

Description

,- , ` 21gO92~

Beiersdorf Aktiengesellschaft Description Germicidal active compound combinations The present invention relates to active compound combinations for protection against microorganisms. It furthermore relates to formulations, preferably cosmetic and dermatological formulations, in particular cosmetic deodorants, comprising such active compound combinations.
It also relates to processes for stabilizing formula-tions, in particular cosmetic and dermatological formula-tions, against attack by microorganisms.
Active compound combinations for protection against microorganisms are used, for example, in formula-tions which are applied to the skin or mucous membrane of a person or an An; ~1 in order to reduce or eliminate microorganism attack on or in the skin or to prevent attack by microorganisms. Such compositions include the terms topical dermatic agents and cosmetics.
However, protection against microorganism attack on formulations themselves, in particular cosmetic and dermatological formulations, is also regarded as protec-tion against microorganisms in the context of the present invention. In technical terms, this protection is called preservation. Preservation in itself is not limited to cosmetic or dermatological formulations. Rather, it relates to protection of all organic materials against microbial degradation.
Cosmetic formulations for protection against microorganisms are primarily deodorants, that is to say formulations which are intended to eliminate body odour.
Body odour is formed when fresh perspiration, which is in itself odourless, is decomposed by microorganisms. During this operation, a large number of highly volatile sub-stances are formed, malodorous isovaleric acid being mentioned only as an example.

- 2140921~

Deodorants:
Cosmetic deodorants of the prior art are based on various action principles.
The formation of perspiration can be suppressed by astringents - aluminium salts, such as aluminium hydroxychloride, are chiefly used. Apart from the fact that the associated denaturing of skin proteins is an undesirable secondary reaction, the substances used for this purpose furthermore intervene in the heat balance of the skin and should at best be used in exceptional cases.
The bacterial flora on the skin may be reduced by antimicrobial substances. In the ideal case, only the microorganisms causing an odour should be destroyed here.
In practice, however, it has been found that the entire microflora of the skin is harmed to the same extent. The microorganisms which cause no odour are occasionally even harmed more severely.
Finally, body odour can also be masked by fra-grances, the classical method which, however, meets the aesthetic requirements of the consumer the least, since the mixture of body odour and perfume fragrance smells rather unpleasant.
Deodorants should meet the following conditions:
(1) The biological processes of the skin should not be impaired.

(2) The deodorants should not have a pronounced intrin-sic smell.

(3) They must be harmless in the event of an overdose or other use not as specified.

(4) They should not become concentrated on the skin after repeated use.

(5) They should be easy to incorporate into commercially available cosmetic formulations.
Both liquid deodorants, for example aerosol sprays, roll-ons and the like, and solid formulations, for example deo sticks, powders, powder sprays, intimate cleansing compositions and the like, are known and customary.
An object of the present invention was thus to develop cosmetic deodorants which do not have the disad-vantages of the prior art. In particular, the deodorants should largely preserve the microflora of the skin, but selectively reduce the microorganisms which are respon-sible for body odour.
Topical dermatic aqents:
Some of the unpleasant or pathogenic germs attack the various layers of the skin, including the acne pathogen Propionibacterium acnes. P. acnes preferentially populates the hair follicles and therefore usually breaks out during puberty of the persons affected. The often considerable skin lesions associated with it are at best unattractive, but may also considerably trouble the patient emotionally.
Lantibiotics have also already been proposed as therapeutics against skin complaints caused microbially, namely acne. A disadvantage is that these formulations are stable for only a short time.
Another object of the present invention was thus to provide formulations and processes which remedy this shortcoming.
Stabilization of perfumed cosmetic formulations:
Cosmetic formulations, that is to say deodorants, having an active content of lantibiotics are known from DE-A 39 38 140. The compositions described therein are distinguished by an outstanding action and tolerability.
However, the cosmetic deodorants described therein have the disadvantage that an addition of perfume constituents reduces the deodorizing activity of the lantibiotics in an undesirable manner in a way which has not yet been clarified exhaustively. Since almost all cosmetics, whether deodorizing or not, comprise perfume constituents, this reduction in action represents a considerable problem.
Another object of the invention was thus to suppress the harmful action of perfume constituents on active compound components in cosmetic formulations.
Description of the invention:
It was astonishing and not foreseeable to the 21~0~20 expert, and herein lies the achievement of all these objects, that combinations of imidazole and/or one or more derivatives of imidazole which can have the follow-ing general structural formula Rl /~\
R2-c\ /~-R~
f N

- wherein the radicals can have the following meaning:
R1 = H or C(1 25) - alkyl, R2 = ~ or C~1 25) - alkyl, R3 = H or C~1 25) - alkyl, R4 = H or C~1 25) - alkyl, - wherein R4 can also, and preferably if R1, R2 and R3 are a hydrogen atom, be the radicals -CH2 -cH2 -NRsR6 and -CH2-CH(NRsR6)-COOR"
wherein Rs = H or C~1 25) - alkyl, R6 = H or C~l 25) - alkyl, R, = H or C~1 25 ) - alkyl, and a lantibiotic or a mixture of two or more lantibiotics - would be stable during storage, - would have a sufficiently high half-life on the skin, - would be suitable for use as a cosmetic, - do not allow interactions between lantibiotics and perfume constituents, - would have a suitable stability when used in cosmetics, - would be active selectively against odour-gener-ating microorganisms, - would preserve the symbiotic microflora of the skin, - would also be fully active when perfume compo-nents are used, - would achieve a significant improvement in the deodorizing action compared with imidazole-free compositions, - would have a suitable stability when used as preservatives, - would have a suitable stability when used in foodstuffs.
In particular, it was astonishing that the compositions according to the invention not only are suitable for cosmetic purposes but moreover are more effective and gentler than the compositions of the prior art.
The invention also relates to the use of one or more derivatives of imidazole which have the following general structural formula R C/ \C R
C N

- wherein the radicals can have the following meaning:
Rl = H or C~l 25) - alkyl, R2 = H or C(l 25) - alkyl, R3 = H or C~l 25 ) - alkyl, R4 = H or C~l 25) - alkyl, - wherein R4 can also, and preferably if Rl, R2 and R3 are a hydrogen atom, be the radicals -CH2 -cH2 -NR5R6 and -CH2-CH(NRsR6)-COOR"
wherein

- 6 -Rs = H or C(l_ 25) - alkyl, R6 = H or C(l 25~ - alkyl, R, = H or C(l 25) - alkyl, as the active principle in cosmetic deodorants.
Lantibiotics per se have been known for many years. They are polypeptides which are synthesized by microorganisms and are distinguished by representatives of the amino acid group of lanthionines as a structural element in the peptide sequence.
The lanthionines have the following structures:
HOOC-CH(NH2)-CH2-S-CH2-CH(NH2)-COOH
also written as:
H2N-ala-S-ala-COOH
l l (meso-lanthionine) and - 15 HOOC-CH(NH2)-CH2-S-CH(CH3)-CH(NH2)-COOH
also written as:

H2N-ala-S-aba-COOH
l l (threo-methyl-lanthionine) Ring structures are formed in the lantibiotics with these lanthionines.
Examples of lantibiotics are nisin, epidermin, subtilin, cinramycin, duramycin, ancovenin, gallidermin and Pep 5.
The abovementioned substances are known per se and can be found under the Chemical Abstracts registry numbers:
Nisin :1414-45-5 Epidermin :99165-17-0 Subtilin :1393-38-0 Pep 5 :110655-58-8 Duramycin :1391-36-2 Ancovenin :88201-41-6 21~092~

Gallidermin : 117978-77-5 Nisin, for example, is a peptide of 34 amino acids synthesized by Streptococcus lactis.
Nisin has the following amino acid sequence (primary structure):

., . I S
H2N-ile-dhb-ala-ile-dha-leu-ala-aba-pro-gly-ala-lys-S

-aba-gly-ala-leu-met-gly-ala-asn^

S
, S
I I
-met-lys-aba-ala-aba-ala-his-ala-S

-ser-ile-his-val-dha-lys-COOH

wherein dhb = dehydrobutyrine dha = dehydroalanine aba = aminobutyric acid E. Gross, J.L. Morell, "The Structure of Nisin", J. Amer.
Chem. Soc. 93, pages 4634-4637 (1971).
The action mechanism of nisin and the lantibiot-ics related to nisin which have essentially the sameaction can be explained as follows: cell walls are destroyed by release of autolysines. Since channels are also formed in the cytoplasm membrane, low molecular weight cell constituents can diffuse out, whereby the (prokaryotic) cell is destroyed.
The accuracy of this explanation, however, is of no relevance to the invention. An attempt is merely being made to explain the microbiological processes.
Eukaryotic cells, that is to say skin cells, fungi and the like, are resistant to nisin and other lantibiotics.
Lantibiotics are practically non-toxic to warm-blooded animals. The LD50 for nisin, for example, is greater than 7 g/kg (determined for rats and cats). It is known that nisin and the other lantibiotics chiefly act against micrococci and coryneform bacteria. In some countries, chiefly in Eastern Europe, it is a substance which is approved as a foodstuffs preservative (not in Germany).
For traditional reasons, lantibiotics are often counted among the so-called "peptide antibiotics".
However, for various reasons they are not to be inter-preted as conventional antibiotics, at least not all their representatives, least of all nisin. Everything suggests, rather, that they should be given the designa-tion "bacteriocins". Bacteriocins are proteins which are produced by bacteria and kill or inhibit the growth of related bacteria species or strains. They are usually coded by plasmids, the so-called bacteriocin factors.
Epidermin is a lantibiotic which has been iso-lated from microorganisms occurring on the human skin.
The use of epidermin as an antibiotic/therapeutic having a topical action is described in EP-A-0 181 578. It is used for combating infectious diseases.
Gallidermin is a lantibiotic which differs from epidermin by only one amino acid. EP-A-0 342 486 cites a cosmetic agent comprising gallidermin, but without cosmetics being disclosed and without the advantageous combination of lantibiotics and imidazole or derivatives thereof being obvious.
International Patent Application W0 89/12399 furthermore discloses combinations of nisin and complex-ing agents and/or emulsifiers for use as preservatives.
Imidazole is characterized by the structural formula - 21~0g20 N j /, C - N

Imidazole is likewise practically non-toxic to warm-blooded An;~-ls, but acts as an antimetabolite against histamine and nicotinic acid in lower Ani~-ls. Certain derivatives of imidazole are used as antimycotics.
Derivatives of imidazole which can likewise be used according to the invention are those of the general structural formula R2-c\\ ,/-R3 C N
/

wherein the radicals can have the following meaning:
Rl = H or C(1 2s) - alkyl, 10 R2 = H or C~l 25) - alkyl, R3 = H or C~l 25) - alkyl, R4 = H or C~l 25) - alkyl, wherein R4 can also, and preferably if Rl, R2 and R3 are a hydrogen atom, be the radicals and -CH2-CH(NR5R6)-COOR"
wherein R5 = H or C(l 25) - alkyl, R6 = H or C(l 25) - alkyl, 20 R, = H or C(l 25) - alkyl.
Among these derivatives of imidazole, those which are water- and/or alcohol-soluble are preferred. Those derivatives in which Rl = H are particularly preferred.

21~092(1 It is particularly advantageous to use the non-derivatized parent substance (R, - R4 = H) of imidazole.
The derivatives histidine / N \
H-C\ /C-H
C N

and histamine H
I

~N ~

C N

H2N-cH2-cH2 are also advantageous.
The activity of selected compounds according to the invention decreases in the following sequence:
Imidazole (unsubstituted) > histamine > histidine It is of course clear to the expert that the use of histamine in products which come into direct contact with the human or animal organism, that is to say, for example, cosmetics and foodstuffs, would not be accept-able, since histamine, as a tissue hormone, can bring about undesirable reactions: histamine occurs in an increased amount with allergies and anaphylaxes.
The use of the combination according to the invention of histamine and lantibiotics should therefore be subject to medical supervision.
The combinations according to the invention are advantageously characterized by a content of 0.01 - 99.99 % by weight of an imidazole component - 2140~2~

99.99 - 0.01 % by weight of an individual substance or a mixture from the group of lantibiotics, based on the total weight of the combination.
The combinations according to the invention are particularly advantageously characterized by a content of 0.1 - 99.9 % by weight of an imidazole component and 99.9 - 0.1 % by weight of an individual substance or a mixture from the group of lantibiotics, based on the total weight of the combination.
The combinations according to the invention are especially advantageously characterized by a content of 1.0 - 99.0 % by weight of an imidazole component and 99.0 - 1.0 % by weight of an individual substance or a mixture from the group of lantibiotics, based on the total weight of the combination.
The lantibiotics are preferably present in the final formulations in concentrations of 0.1 - 10000 ppm.
The lantibiotics are particularly preferably present in the final formulations in concentrations of 0.1 750 ppm, especially preferably in concentrations of 0.5 -400 ppm. The concentration data in each case relate to the content of pure active compound and to the total weight of the composition.
Formulations having an active content of nisin, epidermin and/or gallidermin have proved to be particu-larly advantageous. However, the other lantibiotics mentioned are also particularly suitable for the use according to the invention.
It is especially advantageous to use nisin.
It is possible and, where appropriate, advantageous to employ a mixture of lantibiotics as the active principle of the compositions according to the invention.

It is particularly advantageous to buffer the compositions according to the invention to a pH range of 2.5 - 6.5. It is particularly favourable to choose the pH
in the range of 3.5 - 4.8.
The concentrationæ of imidazole are advantageous-ly 0.01 - 5.00% by weight, based on the total weight of the composition, preferably 0.10 - 2.00% by weight, especially preferably 0.25 - 1.00% by weight.
Compositions which are particularly advantageous are those which comprise combinations having a content of 0.1 - 10000ppm of lantibiotics, in particular nisin, and 0.01 - 5.00% by weight of imidazole, preferably 2.0 - 750ppm of lantibiotics, in particu-lar nisin, and 0.10 - 2.00% by weight of imidazole, particularly preferably 5.0 - 400 ppm of lantibiotics, in particu-lar nisin, and 0.25 - 1.00 % by weight of imidazole, in each case based on the total weight of the formulation.
Those formulations which comprise 0.4 - 0.6% by weight of imidazole or derivatives thereof are particu-larly preferred.
Perfume oils which cause lasting deactivation of lantibiotics in particular are listed in Table 1. How-ever, if lantibiotics are present in combination with imidazole or derivatives thereof, the destabilization is compensated.
Table 1 Aldehyde C12 Hydroxycitronellol Allyl amyl glycolate Isoeugenol 35 Ambrettolide Isoraldein 70 Amyl-cinnAm~ldehyde Jonol Anisaldehyde Lilial (Firmenich) Aurantesin Lyral Benzyl acetate Methyl dihydrojasmonate 214092~

Benzyl salicylate Musk ketone Castoreum p-Hydroxybenzylacetone Cedryl ketone Patchouli oil Eugenol Phenylethyl alcohol 5 Florol (Firmenich) Phenylethyl phenylacetate Gamma decalactone Phenylethyl pivalate Geraniol Tagetes oil Geranium oil Bourbon Terpentine oil Geranyl acetate Vertosine 10 Helosine Ylang-ylang-oil Hexenyl salicylate Zibeth Hydrocarboresin C;nnA~-ldehyde Hydroxycitronellal (Firmenich) Cinnamyl alcohol Apart from the perfume oil labelled otherwise, the perfume oils listed in Table 1 are marketed by the company Haarmann & Reimer.
Stabilization with respect to the substances mentioned in Table 1 is claimed according to the inven-tion, but is not to be limited thereto.
The invention thus also relates to the use of one or more derivatives of imidazole which have the following general structural formula ~N1 R 2 - C, ,C - R 3 - wherein the radicals can have the following meaning:
Rl = H or C(l 25~ - alkyl, R2 = H or C(l 25) - alkyl, R3 = H or C(l 25~ - alkyl, R4 = H or C(l 25) - alkyl, - wherein R, can also, and preferably if Rl, R2 and 21gO92~ .
_ - 14 R3 are a hydrogen atom, be the radicals and -CH2-CH(NR5R6)-COOR"
wherein R5 = H or C(l 25~ - alkyl, R6 = H or C(l 25, - alkyl, R7 = H or C(l 25~ - alkyl, for stabilizing lantibiotics.
The deodorizing cosmetic compositions according to the invention can be in the form of a preparation which can be sprayed from aerosol containers, squeeze bottles or by a pump device, or in the form of a liquid composition which can be applied by means of roll-on devices, but also in the form of a water-in-oil or oil-in-water emulsion, for example a cream or lotion, which can be applied from normal bottles and containers. Other cosmetic deodorants can be in the form of deodorizing tinctures, deodorizing intimate cleansing compositions, deodorizing shampoos, deodorant soap, deodorizing shower or bath formulations, deodorizing powders or deodorizing powder sprays. However, customary deo stick bases can also serve as carriers for solid formulations and sticks.
Customary cosmetic carrier substances which can be employed for preparation of the deodorizing composi-tions according to the invention are, in addition towater, ethanol, isopropanol, glycerol and propylene glycol, skincare fatty or fat-like substances, such as partial glycerides of fatty acid mixtures, oleic acid decyl ester, cetyl alcohol, cetyl stearyl alcohol and 2-octyldodecanol, in the ratios of amounts customary forsuch preparations, as well as mucilaginous substances and thickeners, for example methylcellulose, polyacrylic acid and polyvinylpyrrolidone, and in addition also small amounts of cyclic silicone oils (polydimethylsiloxanes), as well as liquid polymethylphenylsiloxanes of low ViSCOS ity .
Suitable propellants for deodorizing cosmetic compositions according to the invention which can be sprayed from aerosol containers in the form of a spray - 2140~

jet on actuation of the valve are the customary known highly volatile liquefied propellants, for example hydrocarbons (propane, butane and isobutane~, which can be employed by themselves or as a mixture with one another. Compressed air can also advantageously be used, where appropriate.
Emulsifiers which have proved suitable for the preparation of the deodorizing cosmetic compositions according to the invention, which are preferably to be applied to the desired areas of skin as liquid formula-tions by means of a roll-on device, and can be used in the compositions in a small amount tfor example) of 2 to 5% by weight, based on the total composition, are nonionic types, such as polyoxyethylene fatty alcohol ethers, for example cetostearyl alcohol polyethylene glycol ether having 12 or 20 added-on ethylene oxide units per molecule of cetostearyl alcohol, and sorbitan esters and sorbitan ester-ethylene oxide compounds (for example sorbitan monostearate and polyoxyethylene sorbitan monostearate), as well as long-chain higher molecular weight waxy polyglycol ethers.
In addition to the constituents mentioned, it is possible to admix to the deodorizing cosmetic composi-tions according to the invention - the pH of which is preferably brought to 2.5 to 6.5, in particular 3.5 to 4.8, for example, by customary buffer mixtures -perfume, dyestuffs, antioxidants (for example alpha-tocopherol or butylated hydroxytoluene (= 2,6-di-tert-butyl-4-methylphenol in amounts of 0.01 to 0.03%, based on the total composition), suspending agents, buffer mixtures or other customary cosmetic base substances, such as triethanolamine or urea.
Those substances and perfume oils which are stable, do not irritate the skin and already have antibacterial (bacteriostatic) properties as such are also suitable, where appropriate, for perfuming.
In an individual case, however, it is to be weighed up whether the advantage which the highly selec-tive antimicrobial action of the lantibiotics and, in 21~û~2~

particular, of the combinations according to the inven-tion offers is to be reduced or not by other substances which, under certain circumstances, have a less selective action.
However, the invention is not limited to the formulations and compositions, auxiliaries and carrier substances mentioned.
The particular amounts of cosmetic carrier substances and perfume to be employed can easily be determined by the expert by simple trials, as a function of the nature of the particular product.
Apart from specific formulations which are noted in each case separately in the examples, the cosmetic compositions are prepared in the customary manner, usually by simple mixing while stirring, if appropriate with gentle heating. The preparation presents no diffi-culties. For emulsions, the fat phase and the aqueous phase, for example, are prepared separately, if necessary with heating, and then emulsified.
Otherwise, the customary rules for composing cosmetic formulations, with which the expert is familiar, are to be observed.
The combinations according to the invention can be incorporated into the compositions according to the invention in a simple manner. They are preferably added in dissolved form (for example as an aqueous, alcoholic or alcoholic-aqueous solution) to the other consituents of the formulations. However, it is especially advantage-ous to incorporate lantibiotics into so-called powder sprays. It is also advantageous to avoid additives which can harm the natural microflora, since the combinations according to the invention in themselves selectively reduce the odour-generating microorganisms.
If the combinations according to the invention are to be incorporated into powder sprays, the suspension bases for this can advantageously be chosen from the group consisting of aerosil, kieselguhr, kaolin, talc, modified starch, titanium dioxide, zinc oxide, silk powder, nylon powder, polyethylene powder and related substances.
The following examples serve to describe the invention, without the intention being to l;~it the invention to these examples.
Perfume compositions:
Perfume No. 1 Benzyl acetate 4.0% by weight Geraniol 5.0% by weight Phenylethyl alcohol 9.0% by weight Various other odoriferous substances to 100.0% by weight Perfume No. 2 Benzyl acetate 5.4% by weight Geraniol 8.0% by weight Ylang-ylang oil 8.4% by weight Various other odoriferous substances to 100.0% by weight Perfume No. 3 Benzyl acetate 5.0% by weight Geraniol 12.0% by weight Hydroxycitronellal 7.0% by weight Various other odoriferous substances to 100.0% by weight Example 1 Pump spray Nisin (pure substance) 0.025 g Imidazole 5-000 g Ethanol pharm. (96%) 354.875 g Perfume 1 10.000 g Dyestuff as desired Water to1,000.000 g ExamPle 2 Pump spray Epidermin 0.010 g Imidazole 3.500 g Ethanol pharm. (96%) 354.875 g Perfume 1 10.000 g 35 Dyestuff as desired Water -to 1,000.000 g 214û920 ExamPle 3 Deodorant roller (roll-on) 0.150 g Nisin ' 8.000 g Imldazole 5 Hydroxyethylcellulose 5.000 g Propylene glycol 5.000 g Ethanol pharm. (96%) 355.850 g 10.000 g Perfume 2 as desired Dyestuff 10 Water to 1,000.000 g Example 4 Deodorant roller (roll-on) Epidermin 0.120 g Imidazole 6.500 g 15 Hydroxyethylcellulose 5.000 g Propylene glycol 5-000 g Ethanol pharm. (96%) 355.850 g lO.ooo g - Perfume 2 as desired Dyestuff 20 Water to 1,000.000 g Example 5 Spray 0.200 g Nisin Imidazole 1.500 g 25 Ethanol pharm. (96%) 150.000 g 50.000 g Propylene glycol 300.000 g Dimethyl ether 10.000 g Perfume 3 to 1,000.000 g Water Example 6 Spray Epidermin 0.150 g Imidazole 2.000 g Ethanol pharm. (96%) 150.000 g 35 Propylene glycol 50-000 g 300.000 g Dimethyl ether 21~0920 10.000 g Perfume 3 Water to 1,000.000 g ExamPle 7 Spray 0.180 g Nisin 17.000 g Imldazole Ethanol pharm. (96%) 497.160 g 2-Octyldodecanol 2.660 g 10.000 g Perfume 1 Dimethyl ether to 1,000.000 g ExamPle 8 Spray Epidermin 0.150 g Imidazole 13.800 g Ethanol pharm. (96%) 497.160 g 2-Octyldodecanol 2.660 g 10.000 g Perfume 1 Dimethyl ether to 1,000.000 g Example 9 Nisin 1.200 g Imidazole 32.000 g Cetylstearyl alcohol 20.000 g 2-Octyldodecanol 20.000 g ' 200.200 g Kaolln 200.200 g 25 Talc 48.200 g Aerosll 10.000 g Perfume 3 to 1,000.000 g Rice starch Example 10 30 Epidermin 1.000 g 27.000 g Imidazole Cetylstearyl alcohol 20.000 g 2-Octyldodecanol 20.000 g 200.200 g Kaolin 200.200 g 35 Talc 21~092~

Aerosil 48.200 g Perfume 3 10.000 g Rice starch to 1,000.000 g ExamPle 1 1 5 Washing gel concentrate Nisin 9.000 g Imidazole 17.000 g Cocoamidopropylbetaine 613.300 g Tipa-lauryl ether sulphate 306.700 g 10 Sodium chloride as desired Perfume 2 40.000 g Dyestuff as desired Citric acid 1.000 g Glycerol 10.000 g Water to 1,000.000 g Example 12 Washing gel concentrate Epidermin 7-000 g Imidazole 12.000 g Cocoamidopropylbetaine 613.300 g Tipa-lauryl ether sulphate 306.700 g Sodium chloride as desired Perfume 12 40.000 g Dyestuff as desired 25 Citric acid 1.000 g Glycerol 10.000 g Water to 1,000.000 g Example 13 Powder spray I
30 a) Suspension base Polymethylsiloxane (Cyclomethicone) 72.000 g Talc 24.000 g Bentonite gel IPM 3-000 g Nisin - 1.000 g Imidazole 5-000 g 21~û92~

Perfume 1 2.500 g b) Finished spray Suspension base I 20.000 g Propane/butane 80.000 g Example 14 Powder spray II
a) Suspension base Polymethylsiloxane (Cyclomethicone) 72.000 g Titanium dioxide 24.000 g Bentonite gel IPM 3.000 g Nisin 1.000 g Imidazole 8.000 g Perfume 3 2.000 g b) Finished spray Suspension base I 20.000 g Propane/butane 80.000 g ExamPle 15 Powder spray III
a) Suspension base Polymethylsiloxane (Cyclomethicone) 72.000 g Silk powder 24.000 g Bentonite gel IPM 3.000 g Nisin 1.000 g Imidazole 6.000 g Perfume 2 2.000 g b) Finished spray Suspension base I 20.000 g Propane/butane 80.000 g The superiority of the present invention is demonstrated with the aid of the following experiments.
The compositions according to the examples were evaluated 092~

with the aid of the so-called "sniff test".
Experiment 1:
Compositions according to the invention from Example 1 were tested against a placebo, that is to say a composition which is identical apart from the content of active substance.
A group of-30 subjects were told to treat in each case one armpit with composition according to the inven-tion and the other with placebo. The subjects then wore a shirt with slip inserts under the shoulders for three hours. After this period of time, the slip inserts were transferred to separate bottles. The smell of the inserts was evaluated by three test persons. The experiment was carried out as a double-blind experiment, so that neither the subjects nor the test persons knew which armpit had been treated with which composition.
It was found that the formulations cont~;n;ng active compound had a better action when evaluated sensorially than the corresponding placebos in each case in 29 out of 30 cases. In 1 out of 30 cases the test person stated that the treated and untreated samples did not differ from one another.
ExPeriment 2:
Compositions from Example 4 (comprising imidazole, formulations C) according to the invention were tested against compositions identical to these without imidazole (formulations D).
A group of 30 subjects were told to treat in each case one armpit with formulation C and the other with formulation D. The subjects then wore a shirt with slip inserts under the shoulders for three hours. After this period of time, the slip inserts were transferred to separate bottles. The smell of the inserts was evaluated by five test persons. The experiment was carried out as a double-blind experiment, so that neither the subjects nor the test persons knew which armpit had been treated with which composition.
It was found that the formulations C had a better action when evaluated sensorially than formulations D in 2141~92~

each case in 25 out of 30 cases.
In each case in 4 out of 30 cases, formulations D
were evaluated as being better sensorially than formula-tions C.
5In 1 out of 30 cases, the test person stated that the treated and untreated samples did not differ from one another. - -

Claims

Patent claims:

1. Combinations of imidazole and/or one or more derivatives of imidazole which have the following general structural formula - wherein the radicals can have the following meaning R1 = H or C(1-25) - alkyl, R2 = H or C(1-25) - alkyl, R3 = H or C(1-25) - alkyl, R4 = H or C(1-25) - alkyl, - wherein R4 can also, and preferably if R1, R2 and R3 are a hydrogen atom, be the radicals and -CH2-CH(NR5R6)-COOR7, wherein R5 = H or C(1-25) - alkyl, R6 = H or C(1-25) - alkyl, R7 = H or C(1-25) - alkyl, and a lantibiotic or a mixture of two or more lantibiotics.

2. Combinations according to Claim 1, wherein the lantibiotics are chosen from the group consisting of nisin, epidermin, subtilin, cinramycin, duramycin, ancovenin, Pep 5 and gallidermin.

3. Combinations according to Claim 1, wherein the imidazole derivatives are chosen from the group consist-ing of unsubstituted imidazole, histidine and histamine.

4. Combination according to Claim 1, characterized by a content of 0.01 - 99.99 % by weight of an imidazole component and 99.99 - 0.01 % by weight of an individual sub-stance or a mixture from the group of lanti-biotics, based on the total weight of the combination.

5. Formulations comprising combinations according to Claim 1, wherein the lantibiotics are present in a content of 0.1 - 10000 ppm, based on the total weight of the formulations.

6. Formulations comprising combinations according to Claim 1, wherein the lantibiotics are present in a content of 0.1 - 750 ppm, based on the total weight of the formulations.

7. Formulations comprising combinations according to Claim 1, wherein the lantibiotics are present in a content of 0.5 - 400 ppm, based on the total weight of the formulations.

8. Formulations comprising combinations according to Claim 1, wherein the imidazole derivative or derivatives are present in a concentration of 0.01 - 5.00% by weight, based on the total weight of the formulations.

9. Formulations comprising combinations according to Claim 1, wherein the imidazole derivative or derivatives are present in a concentration of 0.10 - 2.00% by weight, based on the total weight of the formulations.

10. Formulations comprising combinations according to Claim 1, wherein the imidazole derivative or derivatives are present in a concentration of 0.4 - 0.6% by weight, based on the total weight of the formulations.

11. Formulations according to one of Claims 1 - 10, characterized in that they are in the form of deodorant sprays, roll-ons, pump sprays, tinctures, intimate cleansing compositions, shampoos, shower or bath formula-tions, powders, powder sprays or deo sticks.

12. Use of one or more derivatives of imidazole which have the following general structural formula - wherein the radicals can have the following .
meaning:
R1 = H or C(1-25) - alkyl, R2 = H or C(1-25) - alkyl, R3 = H or C(1-25) - alkyl, R4 = H or C(1-25) - alkyl, - wherein R4 can also, and preferably if R1, R2 and R3 are a hydrogen atom, be the radicals and -CH2-CH(NR5R6)-COOR7, wherein R5 = H or C(1-25) - alkyl, R6 = H or C(1-25) - alkyl, R7 = H or C(1-25) - alkyl, for stabilizing lantibiotics.

13. Use of combinations according to one of Claims 1 - 3 for combating Propionibacterium acnes.

14. Use of combinations according to one of Claims 1 - 3 for the preparation of a dermatological formulation against acne.