WO2005012210A2

WO2005012210A2 - Antimicrobial active preparations containing terpene derivatives

Info

Publication number: WO2005012210A2
Application number: PCT/EP2004/008605
Authority: WO
Inventors: André RIEKS; Markus KÄHLER; Ulrike Kirchner; Kerstin Wiggenhorn; Mona Kinzer; Sabine Risch
Original assignee: Dr. Andre Rieks - Labor Für Enzymtechnologie Gmbh
Priority date: 2003-08-01
Filing date: 2004-07-30
Publication date: 2005-02-10
Also published as: WO2005012210A3; DE10335634A1; DE10335634B4

Abstract

The invention relates to the use of perillic, geranic and citronella acids, the derivatives thereof and citronrllol derivatives in the form of antimicrobial active agents against bacteria, yeast and/or mildew, microorganisms hereafter. Said invention relates, in particular to the use of said antimicrobial active agents for producing cosmetic and pharmaceutical preparations, food product and animal food compounds. Natural monoterpenes and the derivatives of the oxidation products thereof as the antimicrobial active agents are also disclosed.

Description

Antimicrobial preparations

The present invention relates to the use of perillic acid, geranic acid, citronellic acid and derivatives of geranic acid, citronellic acid, geraniol and citronellol as antimicrobial agents against bacteria, yeasts and / or molds, hereinafter called microorganisms. In particular, the present invention relates to the use of the aforementioned antimicrobial active ingredients for the production of cosmetic or pharmaceutical preparations, and of food and feed compositions. The antimicrobial agents are natural monoterpenes and derivatives of their oxidation products. Natural ingredients of numerous medicinal and spice plants have antimicrobial properties. These ingredients include phenolic compounds such as flavonoids, catechols or coumarins as well as the monoterpenes found in various essential oils.

A common characteristic of many monoterpenes is a more or less distinctive smell. The group of monoterpenes also includes perillic acid, geraniol and geranic acid as well as citronellol and citronellic acid. Perillic acid forms white, slightly aromatic crystals. Geraniol is an oily, aromatic liquid. Geranic acid is a colorless, slightly aromatic liquid that is soluble in ethanol or DMSO and sparingly soluble in water. Citronellol is a clear liquid with a rose-like aroma. Citronellic acid is a clear, slightly aromatic liquid. The chemical formulas of perillic acid, geranic acid, citronellic acid, citronellol and geraniol are shown below:

Perillic acid geranic acid citronellic acid citronellol geraniol

Regarding their antimicrobial properties, these and similar compounds behave very differently despite their similar structure. For example, while the naturally occurring monoterpene limonene has only weak bacteriostatic and almost no bactericidal effects, others Monoterpenes are in part effective bactericides, yeasticides or fungicides. In particular monoterpenes with free hydroxyl groups, such as, for example, Carvol, Carvacrol,

Eugenol, linalool, menthol, terpinen-4-ol, terpineol, thymol and those with aldehyde or keto function, such as

However, according to the literature, carvone or menthone show significant antimicrobial activity, although limited to certain microorganisms (Inouye et al. Journal of

Antimicrobial Chemotherapy 47 (2001) 565-573; Kim et al. Journal of Agricultural and Food Chemistry 43 (1995) 2839-2845). Perilla alcohol was disclosed in DE 692 18 933 T2, which also describes the synthesis of perilla alcohol, as a bacterial and yeast-killing agent. Perillic acid was not mentioned here. DE 27 28 921 C3 proposes the use of farnesol as a bacteriostat in body deodorants because of the specific activity against Corynebacteria and staphylococci, but at an application concentration of at least 0.3% by weight. Farnesol is described herein as ineffective against yeast. Antibacterial activities against gram-negative bacteria (E. coli, Haemophil us infl uenza, Sal onella typhimuri um, Listeria and Vibrio vulnificus) and gram-positive bacteria (Streptococcus pneumoniae, Streptococcus pyogenes and Staphylococcus aureus) have been demonstrated for geraniol (Inouye et al. Journal of An timicrobial Chemotherapy 47 (2001) 565-573).

Alcohols and aldehydes are already known to have antimicrobial activity. For example, ethanol or propanol as well as formaldehyde have been used as preservatives for a long time. The compound phenoxyethanol, which belongs to the phenylhydroxyalkyl ethers, has also long been used as a preservative in the pharmaceutical and cosmetic industry. Eugenol, isoeugenol, citral or hydroxycitral are monoterpenes with free hydroxyl or Aldehyde groups that show antimicrobial activity and are used in cosmetics or pharmaceuticals. However, the use of aldehydic compounds in particular in cosmetics or pharmaceuticals is very unsafe for health. Aldehydes are known contact allergens. For example, allergenic skin reactions were observed for the fragrances anisaldehyde, citral, benzaldehyde, piperonal and perillaaldehyde (Watanabe et al. Journal of Health Science 47 (2001) 327-329). Aldehydes react sensitizing to human skin by forming haptens with skin proteins by forming Schiff bases or via Michael Addition (Dupuis & Benezra. Allergy contact dermatitis to simple chemicals. New York. Marcel Dekker Inc. 1982; Majeti & Suskind Con tact Derma ti tis 3 (1977) 16-18). Numerous studies have shown that cinnamaldehyde as well as cinnamon alcohol, which is converted into cinnamaldehyde by the skin's own enzymes, have a skin-sensitizing effect, but cinnamic acid does not (Cheung et al. Journal of Dermatological Science 31 (2003 9-19) Guinea pig skin with cinnamaldehyde showed guinea pigs 15 times lower cross-reactions with cinnamon alcohol than with cinnamaldehyde and even 25 times lower cross-reactions with cinnamic acid than with cinnamaldehyde (Weibel et al. Acta Dermati ca Venereol. 69 (1989) 302-307). The monoterpene calls perilla aldehyde in contrast to perillic acid, it causes skin irritation (Okazaki et al. Skin Research 24 (1982) 250-256). Motoyoschi et al. (Cosmetics & Toiletries 94 (1979) 41-48) showed that the monoterpenes used as perfume components are Linalool. Geraniol, Citral and citronellol have a significantly greater skin-irritating potential than the esters linalyl acetate or geranyl acetate. Because of their significantly lower allergenic and skin-sensitizing potential, monoterpenic acids or derivatives of monoterpenic acids or alcohols would represent particularly attractive antimicrobial compounds.

In vegetable oils, monoterpenes occur especially as alcohols or aldehydes. Lemongrass essential oil consists of approximately 70% citral, coriander oil 74% linalool, cinnamon oil approximately 60% cinnamaldehyde and geranium oil 30% citronellol and 10% linalool. Monoterpenic acids accumulate in plants only in small percentages. Because of the problems mentioned above when using alcohols and aldehydes, the use of most essential oils in cosmetics should be rejected and the application of defined monoterpenic acids should be preferred.

In contrast to monoterpenes with free alcohol, aldehyde or keto groups, monoterpenic acids, which include, for example, perillic acid, citronellic acid or geranic acid, derivatives of monoterpene alcohols and derivatives of monoterpenic acids are almost not associated with antimicrobial effects in the literature. The aromatic monoterpene carvacrol has a hydroxyl group which has been found to be essential for the antimicrobial activity of the compound. However, neither the methyl ester of carvacrol nor cymen, which differs from carvacrol in that it lacks the hydroxyl group, has no antimicrobial activity (ültee et al. Applied and Environmen tal Microbiology 68 (2002) 1561-1568). The antibacterial effect of citronellic acid has so far only been described against Mycobacteri um tuberculosis (0. Okuda & KK Soran, Fragrance Chemistry Comprehensive Bibliography II, 1968; 1.15, p. 1140). In US Pat. No. 5,658,584 an antimicrobial formulation consisting of a Mixture of hinokitiol and citric acid suggested for use in toilet and household items. There were no antimicrobial activities of the single substance

Citronellic acid also described other monoterpenic acids or their antimicrobial effects. No antimicrobial effects against microorganisms that cause dandruff, dermatomycoses, body odor or acne are described.

It has long been known that bacteria, yeasts and molds change organic materials in an undesirable manner, especially when they are exposed to moisture or air. Cosmetic and pharmaceutical preparations such as ointments, creams, hydrogels, emulsions, pastes, tinctures, pump sprays, toothpastes, cleansing milks or juices are at risk, as are foods or technical products, for example wall paintings or paints. Preparations, foods or products that are either themselves watery or that are exposed to moisture in the course of their formation, storage or use are particularly at risk.

The decomposition of carbohydrates, proteins or fats in such products can already be recognized externally by the appearance of cloudiness, coloring and strange smells, the formation of mold lawn or the rising of bubbles. The infestation with microorganisms often leads not only to changes in the external appearance, but also to the quality of the infected product. Many microorganisms not only destroy valuable ingredients, but also produce harmful metabolic products. In cosmetics, for example, skin-irritating substances can develop through the decomposition of fats or oils. Such product contamination with metabolic products can be caused by gram-negative or gram-positive bacteria, by yeasts or by mold. Gram-negative bacteria include, for example, Escherichia coli, Salmonella typhimuri um or Pseudomonas aeruginosa. The gram-positive bacteria include Bacillus subtilis, Staphylococcus aureus or Micrococcus varians. Molds are, for example, watering can, brush or bread mold types from the class of the askomycetes or head mold types from the class of the zygomycetes. Known yeasts are, for example, Candida albicans or Saccharomyces cerevisiae.

In order to prevent or delay undesired changes caused by these organisms, preservatives are therefore added to the products; these are antimicrobial, the term antimicrobial both for the inhibition of the growth and the multiplication of microorganisms and for the killing of existing microorganisms.

Numerous synthetic preservatives, e.g. in cosmetics, however, show a high allergy potential. For example, formaldehyde or formaldehyde releasers irritate the mucous membranes and eyes, age the skin and have been shown to be carcinogenic and allergenic in animal experiments.

Halogen-organic preservative compounds with chlorine, bromine, fluorine or iodine are often irritating to the skin and can trigger allergies. Some of these compounds accumulate in the environment and in adipose tissue in humans and are suspected of being carcinogenic. The allergenic and skin-sensitizing potential, in particular of compounds, including monoterpenes, with a free aldehyde group has already been discussed above.

Another major problem in the selection of suitable preservatives is that antibacterial compounds normally have no activity against yeasts or fungi, while compounds which act against yeasts and fungi are not or have little antibacterial activity. This phenomenon is found in many antibiotics. Antibacterial antibiotics such as ampicillin or streptomycin are ineffective against fungi, while yeast or mold-killing substances such as nystatin or clotrimazole are ineffective against bacteria. The common preservative phenoxyethanol works especially against gram-negative bacteria and only inadequately against many gram-positive bacteria.

It is known from the cosmetics industry that there are hardly any antifungal compounds effective against the Aspergillus mold, especially against Aspergillus. For the monoterpene citral, antimicrobial activity against the molds Microsporum gypseum, Aspergillus fumiga tus various types of Pe-nicilliu-m and Tri chophyton mentagrophytes have been described (Dünn. Honors thesis, University of Adelaide (1998); Balacs. I. Journal Aromatherapy 4 ( 1993) 25), but not against Aspergill us niger.

Antimicrobial agents that act simultaneously against gram-negative bacteria, gram-positive bacteria, yeasts and mold are therefore of great interest. Of particular interest are those antimicrobial substances which are also effective against molds such as Aspergillus, preferably those of natural origin. It is therefore a preferred object of the present invention to provide compounds and compositions which are active against bacteria, yeasts and / or molds, preferably compounds which are simultaneously active against bacteria, yeasts and molds.

Another important aspect is the cosmetic or pharmaceutical treatment of dandruff-causing microorganisms. Lipophilic yeast species, especially Malassezia for (formerly Pi tyrosporum ovale) in the mycelium form are responsible for skin changes associated with the formation of dandruff. This organism settles in particular in skin areas with high concentrations of free, long-chain fatty acids. If the sebum glands on the hairy head or face, for example, increasingly excrete sebum (sebum), undesirable and sometimes pathological skin changes can occur as a result of Malassezia furfur being colonized in these regions. Such skin changes are, for example, Pi tyrlasis versi color (bran fungus), Seborrhoea oleosa and Seborrhoea si cca, in particular in the form of dandruff (Seborrhoea capi tis) or Pityrosporum folliculitis. People with such skin scales are usually treated with keratolytic or anti-inflammatory, proliferation-inhibiting (cell division-inhibiting) preparations. Proliferation-inhibiting preparations often contain malodorous active substances, for example tar preparations, or controversial metal compounds such as cadmium, zinc or selenium salts from a health and / or environmentally relevant point of view. The sole use of a keratolytic, for example salicylic acid, has only the detachment of the currently existing dandruff Do not follow and eliminate the real cause of dandruff.

On the other hand, the use of antimicrobial agents for the cosmetic or pharmaceutical treatment of yeast causing dandruff is particularly attractive, since these agents combat the actual cause of dandruff formation. Such antifungal agents currently used also include the metal compounds, such as cadmium, zinc or selenium salts, which are controversial from a health and / or environmental point of view, or unpleasant-smelling essential oils such as thyme or rosemary oil.

It is therefore a preferred object of the present invention to provide compounds and compositions which act against the dandruff-causing yeast Malassezia furfur, can be used in cosmetic or pharmaceutical preparations against the dandruff-causing yeast Malassezia furfur and which are known from the prior art Do not have disadvantages.

Another problem to be solved is the cosmetic or pharmaceutical treatment of certain dermatomycosis causing microorganisms. The specialist speaks of dermatomycoses when certain types of fungus penetrate the skin, hair, hair follicles as well as fingernails and toenails and consequently symptoms such as blisters, redness, peeling, cracks or erosions, often associated with itching or allergic eczema. For example, yeast mycoses can be caused by facultatively pathogenic Candida species. Mold mycoses occur as a result of infection with, for example, Aspergillus species. In principle, dermatomycoses can be combated with antifungal antibiotics. Topically administered antibiotics, however, impair the physiological skin flora to a great extent and thus hinder the natural skin healing process. Furthermore, many pathogenic fungi now show unpredictable resistance to antibiotics, so that such treatment of dermatomycoses is not recommended. Dermatomycoses are treated pharmaceutically with formulations which contain, for example, menthol, salicylic acid or cresol. However, these compounds smell strongly and irritate the skin to the point of triggering pain.

Because of these disadvantages of the prior art, it is a preferred object of the present invention to provide new and not previously used compounds and compositions which are antifungal against Candida and / or against Aspergillus species and are used in cosmetic ^'or pharmaceutical preparations against dermatomycoses can.

In connection with the provision of antimicrobially active preparations, the cosmetic or pharmaceutical prevention and / or treatment of microorganisms causing body odor also plays a special role. Deodorants are used to prevent or treat unpleasant body odors, which are caused by the action of certain skin bacteria on the initially almost odorless sweat due to the formation of strong-smelling decomposition products. On the one hand, molecules are used which only absorb or mask odors, but do not prevent the actual microbial decomposition of sweat. to To combat unpleasant body odors, on the other hand, antiperspirants are also used, which prevent or strongly inhibit perspiration, such as the aluminum or zirconium salts, which act as astringents. The effectiveness of the above-mentioned antiperspirants is based on the formation of poorly soluble precipitates, which block the outlets of eccrine sweat glands and consequently suppress the sweat flow. While zirconium salts can form toxic aerosols when used as a pump spray, skin irritation, redness and itching are frequently observed when using aluminum salts, especially acidic aluminum salts. In contrast to antiperspirants, cosmetic or pharmaceutical agents with a deodorant effect are a class of agents which do not affect the volume of sweat, but, because of their antimicrobial action, kill the bacteria involved in the decomposition of sweat. Coryneform bacteria, especially the bacterial species Corynebacteri um xerosis, play a major role in the development of unpleasant body odors. Phenol derivatives with or without halogen substituents, quaternary ammonium compounds or organic mercury compounds are increasingly being critically questioned in the cosmetics industry as antimicrobial agents against Corynebacteri um xerosis. In particular, the widely used halogenated phenol derivatives are considered to be harmful to health and often have an unpleasant phenolic smell. The terpene farnesol is used, especially in combination with phexoxyethanol, as an antimicrobial additive to deodorant formulations. Farnesol, however, is not particularly effective against gram-positive bacteria, which also include body odor-causing corynebacteria, in concentrations below 0.5%. Another problem is that farnesol has skin-irritating and allergenic potential.

It is therefore a preferred object of the present invention to provide antimicrobial compounds and compositions for the cosmetic or pharmaceutical prevention and / or treatment of body odor-causing microorganisms which do not have the aforementioned disadvantages.

Another important aspect relates to the cosmetic or pharmaceutical treatment of acne-causing microorganisms. The skin disease acne is characterized by inflammatory or non-inflammatory nodules, starting from blocked hair follicles, which can lead to the formation of blackheads (comedones), pustules, abscesses or scars. The most common manifestation, acne vulgaris, occurs mainly during puberty. The causes of acne vulgaris include the cornification and constipation of the hair follicle mouths, an increased production of taig and the production of ^" tissue-damaging enzymes and free fatty acids by the anaerobic, gram-positive, coryneform bacterium Propionibacteri um acnes. Consequences of the metabolic activities of Propionibacteri um acnes are the activation of Complement cascade and the triggering of inflammatory reactions. In topical acne treatment, in addition to strong skin-irritating comedolytic retinoids, for example tretinoin, in particular antibacterial active substances against Propionibacteri um acnes are used. It is not advisable to administer antibiotics at present, since resistance to the usual antibiotics is advisable , such as erythromycin or clindamycin, are frequently observed in Propionibacterium acnes Antibacterial compounds are benzoyl peroxide or azelaic acid. A topical application of benzoyl peroxide leads to skin irritation such as burning, reddening or scaling in many sufferers. In addition, the strong oxidizing agent benzoyl peroxide bleaches hair and clothing. Azelaic acid is less irritating to the skin, but also shows significantly lower antibacterial activities against Propionibacterium acnes. The use of terpenes to treat acne vulgaris has hardly been described. Only the use of a formulation of indole and a natural substance, for example farnesol, citronellol or limonene, is mentioned in US Pat. No. 5,453,276 for the treatment of Propionibacterium acnes. Monoterpenic acids, geraniol or derivatives of geranic acid, citronellic acid, geraniol or citronellol are not described. US Pat. No. 5,175,190 describes the treatment of skin injuries using various acids, including geranic acid. The underlying effect is not antimicrobial but based on cell lysis, triggered by the application of formulations with over 7% acid. In the given concentration, topical application of acids is not recommended due to the tissue-damaging potential. In U.S. Patents 6,423,329, 6,344,218, 5,411,742 and 5,082,656, geraniol is suggested as an additive to acne treatment agents. Geraniol is only used as a perfume or penetration enhancer and not as an antimicrobial agent. In previous patent applications, the use of various naturally occurring compounds, for example Totarol (JP-A-311019), Sempervirol (JP-A-1-311020) or Ferruginol (JP-A-1-311018), was proposed for the treatment of acne vulgaris , However, these substances can only be used to a limited extent, since the natural sources used for their recovery only contain traces of these components. It is therefore a preferred object of the present invention to provide new antimicrobial compounds and compositions for the cosmetic or pharmaceutical treatment of the acne-causing bacterium Propionibacterium acnes which do not have the disadvantages known from the prior art.

The tasks are solved by using perillic acid, geranic acid, citronellic acid and compounds derived from geranic acid, citronellic acid, geraniol and citronellol, such as esters, amides and hydroxycarboxylic acid amide esters.

In particular, the uses according to claims 1 to 25 and the preparations and agents according to claims 26 to 30 are proposed as solutions. The use of compounds which are simultaneously active against bacteria, yeasts and molds, and cosmetic, dermatological and pharmaceutical preparations, foods and crop protection agents and industrial preparations containing these compounds are also part of the invention. Also part of the invention is the use of the compounds which are effective against dandruff-causing and / or dermatomycosis and / or body odor and / or acne-causing microorganisms, and cosmetic, dermatological or pharmaceutical preparations containing these compounds.

The invention relates in particular to compounds of the general formula I.

where R is CRVo (CO) R ³ , COOR ⁴ , CONR ⁵ R ⁶ , COO (CH ₂ ) _n CONR ⁷ R ⁸ , COR ^s or COO (CH ₂ ) _n COR 1 ^l 0 ^u , where

X-Z denotes a single C-C bond or a C = C double bond, i.e. X-Z is CH-CH2 or C = CH and

R ¹ and R ^{2 are} each independently hydrogen or a linear or branched alkyl radical,

R ^{3 is} hydrogen or a linear or branched alkyl radical, alkenyl radical, alkynyl radical, a cycloaliphatic radical, a mono-, di-, tri- or polycyclic aryl radical, an alkyl radical of a branched or unbranched, saturated or unsaturated mono -, Di-, Tri-, or polycarboxylic acid or fatty acid, which is optionally hydroxylated, sulfonated or aminated one to more times,

R ^{4 is} a linear or branched alkyl radical, alkenyl radical, alkynyl radical, a cycloaliphatic radical, a mono-, di-, tri- or polycyclic aryl radical, an alkyl radical of a branched or unbranched, saturated or unsaturated mono -, Di-, tri-, or polycarboxylic acid, which is optionally hydroxylated once to several times,

R ⁵ and R ⁶ each independently of one another are hydrogen, an alkyl, a hydroxyalkyl, aminoalkyl, alkylaminoalkyl, Are dialkylaminoalkyl, sulfoalkyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl or carboxyalkyl radicals, the alkyl radical being a linear or branched alkanyl, alkenyl, alkynyl radical, an aromatic or cycloaliphatic radical,

n is an integer from 1 to 22 and

R ⁷ and R ^{8 are} independently hydrogen, an alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, sulfoalkyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxyalkyl or carboxy radical, the alkyl radical being a linear or branched alkanyl, alkenyl, alkynyl radical, an aromatic or cycloaliphatic radical or R ⁷ and R ⁸ together form a cyclic system which optionally also contains the heteroatoms 0, S, N and optionally one to more times by linear or branched alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxy, carboxy, alkoxycarboxy, aminocarbonyl groups,

R ⁹ and R ^{10 are} each the residue of an amino acid which is bonded to the carbonyl carbon atom via its NH ₂ group,

as well as salts thereof.

According to a preferred embodiment of the invention is / are in the above formula

R ^{3 is} hydrogen or a linear or branched alkanyl radical with a chain length of 1 or 3 to 8 carbon atoms from the group consisting of methyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, a linear or branched alkenyl radical from the Group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl, citronellyl, geranyl, a linear or branched alkynyl radical from the group consisting of propyl, 2-butyl, 3-butylyl, 2-pentmyl, or the rest of a branched or unbranched, saturated or unsaturated polycarboxylic acid with a length of 2 to 5 carbon atoms from the group consisting of oxalic acid, ethyl oxalic acid, malonic acid, succinic acid, glutaric acid or the rest of a hydroxy acid with a length of 2 to 5 carbon atoms. Atoms from the group consisting of glycolic acid, lactic acid, malic acid, hydroxybutyric acid, glyceric acid, hydroxypropionic acid, citric acid, isocitric acid or tartaric acid, or the rest of an amino acid from the group consisting of alanine, glyc n or glutamm,

R ^{4 is} a linear or branched alkanyl radical with one

Chain length of 1 to 8 carbon atoms from the group consisting of methyl, ethyl, hydroxyethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, a linear or branched alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl, citronellyl, geranyl, a linear or branched alkmyl radical from the group consisting of propyl, 2-butyl, 3-butyl, 2-pentmyl, or the remainder of a branched or unbranched, saturated or unsaturated mono- or polycarboxylic acid which is hydroxylated one to five times, the carboxylic acid from the group consisting of glycolic acid, Lactic acid, malic acid, hydroxybutyric acid, glyceric acid, hydroxypropionic acid, citric acid, isocitric acid is selected,

R ⁵ and R ^{6 are} each independently hydrogen, a linear or branched alkanyl, alkenyl, or alkynyl radical with a chain length of 1 to 8 carbon atoms, where the alkanyl radical from the group consisting of methyl, ethyl, hydroxyethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, the alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl and the alkynyl radical from the group consisting of propyl, 2-butyl, 3 -Butmyl, 2-Pentmyl is selected

R ⁷ and R ⁸ independently of one another are hydrogen, a linear or branched alkanyl, alkenyl or alkynyl radical with a chain length of 1 to 5 carbon atoms, the alkanyl radical being selected from the group consisting of methyl, ethyl, hydroxyethyl, Propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, the alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl and the alkynyl radical from the group consisting of propyl, 2-butmyl, 3- Butmyl, 2-Pentιnyl is selected.

Here and below, both the R and S configurations of the compounds and mixtures thereof, including racemic mixtures, are included. In the drawing Be ^¬ R / S thus denotes both the R and S configuration of compounds and mixtures of these, including racemic mixtures.

Insofar as the compounds according to the invention are capable of salt formation, the term “salts” essentially means acid addition salts or salts with inorganic acids, but also salts with bases. Especially water-soluble salts with acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, carbonic acid, sulfur ^¬ acid, toluenesulfonic acid are preferred. Examples of preferred basic Salts are lithium, sodium, potassium, calcium, aluminum, magnesium and ammonium salts.

The invention relates in particular to compounds of the formula I derived from geraniol or citronellol, in which R is CR ¹ (R ² ) 0 (CO) R ³ , where R ¹ , R ² and R ^{3 have} the meaning given above.

According to a first aspect, the invention thus relates to esters of the formula II

II

in which

X-Z has the above meaning,

R ¹ and R ^{2 have} the above meaning and

R is hydrogen or a linear or branched alkyl radical, alkenyl radical, alkynyl radical, a cycloaliphatic radical, a mono-, di-, tri-, or polycyclic aryl radical, an alkyl radical of a branched or unbranched, saturated or unsaturated ^¬ saturated Mono-, di-, tri- or polycarboxylic acid or fatty acid, which is optionally hydroxylated, sulfonated or aminated one to more times,

as well as salts thereof. In the context of the present invention, “linear or branched alkyl radical” is understood to mean a hydrocarbon radical of the general formula C _n H _{2n +} . The residues methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. Are explicitly included. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, hexyl, decyl, dodecyl, eicosanyl and octacosanyl.

Non-limiting examples of a linear or branched alkenyl according to the invention are propenyl, 2-butenyl, 3-butenyl, 3-pentenyl, 1, 3-hexadienyl and others, i.e. for a hydrocarbon residue which contains one or more C-C double bonds.

'Alkynyl' stands for e.g. Propynyl, 2-butynyl, 3-butynyl, 4-hexynyl, 1-decynyl, etc., i.e. for a hydrocarbon radical containing one or more C-C triple bonds.

It is understood that hydrocarbon residues are also included which contain both double and triple bonds.

Cycloaliphatic radicals are generally understood to mean cyclic aliphatic hydrocarbon ring systems which are optionally mono- or polysubstituted, e.g. by alkyl, halogen, hydroxyl and / or amino groups.

The term Αryl 'can be mono-, di-, tri-, or polycyclic aryl such as phenyl, naphthyl, indenyl, fluorenyl, biphenylyl, indacenyl, inter alia, be and generally designated single aromatic carbon rings, or fused aromatic ring systems optionally substituted one or more ^¬ times are substituted, such as by alkyl, halogen, hydroxyl and / or amino groups. Non-limiting examples of the branched or unbranched, saturated or unsaturated mono-, di-, tri- or polycarboxylic acids or fatty acids mentioned above and below are:

Formic acid, acetic acid, propanoic acid, butyric acid, valeric acid, hexanoic acid, sorbic acid, ascorbic acid, lauric acid, palmitic acid, stearic acid, heptanoic acid, octane acid, pelagonic acid, stearic acid, oleic acid, palmitic acid, amic acid, lamic acid, lmoleic acid, lmoleic acid - Steric acid, malonic acid, malic acid, fumaric acid, phthalic acid, adipic acid, pimelic acid, azelaic acid or sebacic acid.

In addition, the abovementioned acids can also be hydroxylated once to five times. Examples of such acids include Glycolic acid, lactic acid, malic acid, hydroxybutyric acid, tartaric acid, citric acid, isocitric acid and glyceric acid.

Furthermore, the aforementioned acids can also be sulfonated or aminated, i.e. wear a sulfo or ammo group. Examples of sulfonated acids include Sulfoacetic acid, 3-sulfopropanoic acid, 3-sulfobutanoic acid, homocystic acid, etc. Examples of aminated acids are amino acids such as Glycm, Alanin, Glutamm and others.

According to a preferred embodiment of the invention, R ^{3 is} hydrogen or a linear or branched alkanyl radical with a chain length of 1 or 3 to 8 carbon atoms from the group consisting of methyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, a linear or branched alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl, citronellyl, geranyl, a linear or branched Alkynyl radical from the group consisting of propynyl, 2-butynynyl, 3-butynyl, 2-pentynyl, or the radical of a branched or unbranched, saturated or unsaturated polycarboxylic acid with a length of 2 to 5 carbon atoms from the group consisting of oxalic acid , Ethyl oxalic acid, malonic acid, succinic acid, glutaric acid or the rest of a hydroxy acid with a length of 2 to 5 carbon atoms from the group consisting of glycolic acid, lactic acid, malic acid, hydroxybutyric acid, glyceric acid, hydroxypropionic acid, citric acid, isocitric acid or the rest of a tartaric acid, or Amino acid from the group consisting of alanine, glycine or glutamine.

The invention further relates in particular to compounds of the formula I derived from geranic acid or citronellic acid, in which R is COOR ⁴ , where R ^{4 has} the meaning given above.

This particularly includes esters of formula III

III

one where

X-Z has the above meaning,

R ^{4 is} a linear or branched alkyl radical, alkenyl radical, alkynyl radical, a cycloaliphatic radical, a mono-, di-, tri- or polycyclic aryl radical, an alkyl radical is branched or unbranched, saturated or unsaturated mono-, di-, tri-, or polycarboxylic acid, the carboxylic acid being optionally hydroxylated to multiple, and salts thereof.

Examples of linear or branched alkyl radicals according to the invention are: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, hexyl, decyl, dodecyl, eicosanyl and octacosanyl.

Non-limiting examples of a linear or branched alkenyl according to the invention are propenyl, 2-butenyl, 3-butenyl, 3-pentenyl, 1,3-hexadienyl and others, i.e. for a hydrocarbon residue that contains one or more C-C double bonds.

Αlkmyl 'stands for e.g. Propyl, 2-butyl, 3-butyl, 4-hexyl, 1-decyl, etc., i. for a hydrocarbon residue containing one or more C-C triple bonds.

'Cycloaliphatic radicals' are generally understood to mean cyclic aliphatic hydrocarbon ring systems which are optionally mono- or polysubstituted, e.g. by alkyl, halogen, hydroxyl and / or ammo groups.

'Aryl' can be mono-, di-, tri- or polycyclic aryl such as, for example, phenyl, naphthyl, indenyl, fluorenyl, biphenylyl, indacenyl and the like generally single aromatic carbon rings or condensed aromatic ring systems which are optionally mono- or polysubstituted, such as by alkyl, halogen, OH and / or NH ₂ groups.

As already mentioned, the mono-, di-, tri- or polycarboxylic acids mentioned above can be hydroxylated once or several times. Particularly suitable examples em to five times hydroxylated carboxylic acids, especially glycolic acid, lactic acid, malic acid, hydroxybutyric acid, tartaric acid, lemon ^¬ acid, Isozitronensaure and Glycermsaure.

According to a preferred embodiment of the invention, R em is a linear or branched alkanyl radical with a chain length of 1 to 8 carbon atoms from the group consisting of methyl, ethyl, hydroxyethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl, citronellyl, geranyl, alkmyl radical from the group consisting of propyl, 2-butynyl, 3-butylmyl, 2-pentmyl, or the remainder of a branched or unbranched, saturated or unsaturated mono- or polycarboxylic acid which is hydroxylated from one to five times, the carboxylic acid from the group consisting of glycolic acid, lactic acid, malic acid, hydroxybutyric acid, gylcermic acid, Hydroxypropionic acid, citric acid, isocitric acid is selected. According to a further embodiment, the invention relates to amides of the formula IV

IV,

at them

X-Z has the above meaning and

R ⁵ and R ^{6 have} the meaning given above

Amides in which R ⁵ and R ⁶ independently of one another are hydrogen, an alkyl, a hydroxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, sulfoalkyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl or carboxyalkyl radical are particularly preferred are, where the alkyl radical, as already explained in detail above under formula III, can be a linear or branched alkanyl, alkenyl, alkynyl radical, an aromatic or cycloaliphatic radical.

Hydroxyalkyl stands for an alkyl radical mentioned above which is hydroxylated. For example, hydroxyethyl may be mentioned here.

Aminoalkyl-, alkylaminoalkyl-, dialkylaminoalkyl each represent an alkyl radical mentioned above which carries an amino group which can be mono- or dialkylated. Examples are the aminoethyl and the dimethylaminoethyl radical. Sulfoalkyl is understood to mean an alkyl radical mentioned above which bears a sulfo group. One example is the sulfoethyl radical.

Alkoxyalkyl stands for an alkyl radical mentioned above, to which an alkoxy group is bonded. Examples of this are the ethoxyethyl and the ethoxypropyl radical.

Alkoxycarbonyl stands for a carbonyl radical to which an alkoxy group is attached. Examples are the methoxycarbonyl and the ethoxycarbonyl radical.

Alkoxycarbonylalkyl stands for an alkyl radical mentioned above to which an alkoxycarbonyl group is bonded. Examples of this are the ethoxycarbonylmethyl and the methoxycarbonylmethyl radical.

Examples of preferred compounds are:

Geraniumsäureamid, N-Methylgeraniumsäureamid, N, N-Dimethylgeraniumsäureamid, N-Ethylgeraniumsäureamid, N, N-Diethylgeraniumsäureamid, N-Hydroxyethylgeraniumsäureamid, N, N-Di (Hydroxyethyl) geraniumsäureamid, N-Ethoxycarbonyl- geraniumsäureamidhid, N Methoxycarbonyl-methyl geranic acid amide.

Other examples are:

Citronellic acid amide, N-methylcitronellic acid amide, N, N-dimethylcitronellic acid amide, N-ethylcitronellic acid amide, N, N-diethylcitronellic acid amide, N-hydroxyethylcitronellic acid amide, N, N-di (hydroxyethyl) citronellic acid amide, N-ethoxycarbonyl-diethylamide, nitronic acid amide, methoxycarbonyl-methylcitronellsäureamid. According to a preferred embodiment of the invention, R and R ^{δ are} each independently hydrogen, a linear or branched alkanyl, alkenyl or alkynyl radical with a chain length of 1 to 8 carbon atoms, the alkanyl radical from the group consisting of methyl, ethyl, hydroxyethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, the alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl and the alkynyl radical from the group consisting of propynyl, 2-butyninyl, 3- Butninyl, 2-pentinyl is selected.

A further embodiment of the invention relates to hydroxycarboxylic acid amide esters of geranic acid and citronellic acid of the formula V.

v,

at them

X-Z has the meaning given above,

n is an integer from 1 to 22 and

R ⁷ and R ^{8 have} the meaning given above,

as well as salts thereof Particularly preferred are hydroxycarboxylic acid amide esters of geranic acid and citronellic acid, in which R ⁷ and R ⁸ independently of one another are hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, sulfoalkyl, alkoxyalkyl, alkoxycarbonyl,

Alkoxycarbonylalkyl, carboxyalkyl or carboxy radical, where the alkyl radical, as already explained in detail above for formula III, is a linear or branched alkanyl, alkenyl, alkynyl radical, an aromatic or cycloaliphatic radical, or R ⁷ and R ⁸ together form a cyclic system which optionally also contains the heteroatoms 0, S, N and optionally one to more times by linear or branched alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyl, carboxy, alkoxycarboxy, aminocarbonyl Groups is substituted.

Examples of such a cyclic (substituted) system include Pyrrolidine, piperidine, morpholine, 4-piperidine and piperazine.

Examples of preferred compounds are:

Glycolamide geranylate, N-hydroxyethylglycolamide geranylate, N-aminoethylglycolamide geranylate, N-methylglycolamide geranylate, N-ethylglycolamide geranylate, N, N-dimethylglycolamide geranylate and N, N-diethylglycolamide geranylate as well

Glycolamide citronellate, N-hydroxyethylglycolamide citronellate, N-aminoethylglycolamide citronellate, N-methylglycolamide citronellate, N-ethylglycolamide citronellate, N, N-dimethylglycolamide citronellate and N, N-diethylglycolamide citronellate.

According to a preferred embodiment of the invention, R and R ^{8 are} independently hydrogen, is a linear or branched alkanyl, alkenyl or alkynyl radical with a chain length of 1 to 5 carbon atoms, the alkanyl radical from the group consisting of methyl, ethyl, hydroxyethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, the alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl and the alkynyl radical from the group consisting of propynyl, 2-butninyl, 3- Butninyl, 2-pentinyl is selected.

Another embodiment of the invention relates to amides of geranic acid and citronellic acid of the formula VI

VI,

at them

X-Z has the meaning given above,

R ^{9 is} the residue of an amino acid which is bonded to the carbonyl carbon atom via its NH ₂ group,

as well as salts thereof.

The amino acids are preferably glycine, alanine, cysteine, serine, threonine, lysine, aspartic acid and glutamic acid.

A further embodiment of the invention relates to hydroxycarboxylic acid amide esters of geranic acid and citronellic acid of the formula VII

VI I,

at them

X-Z has the meaning given above,

n is an integer from 1 to 22 and

R, 10 is the residue of an amino acid which is bonded to the carbonyl carbon atom via its NH ₂ group,

as well as salts thereof.

The invention accordingly also relates to all derivatives of geranic acid, citronellic acid, geraniol and citronellol according to formulas II to VII which are active against bacteria and / or yeasts and / or molds.

The invention relates in particular to all those compounds which work better against bacteria and / or yeasts and / or molds than R / S limonene and / or geraniol and / or citronellol.

Preferred compounds according to formula II are, for example: Esters of geraniol and a branched or unbranched, saturated or unsaturated mono-, di-, tri- or polycarboxylic acid or polyfatty acid, which is optionally hydroxylated, sulfonated or amidated, and esters of citronellol and a branched or unbranched, saturated or unsaturated mono-, Di-, tri- or polycarboxylic acid or fatty acid, which is optionally hydroxylated, sulfonated or amidated.

Examples of such preferred esters of geraniol are: geranyl malate, geranyl succat, geranyl butyrate, geranyl tartrate, geranyl citrate, geranyl glycolate or geranyl glycerate.

Examples of such preferred esters of citronellol are:

Citronellylmalate, Citronellylsuccmat, Citronellylbutyrat, Citronellyltartrat, Citronellylcitrat, Citronellylglycolat or Citronellylglycerat.

Preferred compounds according to formula III are: esters of ^geranic acid with a linear or branched or cyclic alkyl radical or carboxyalkyl radical of a ^carboxylic or aromatic radical and esters of ^citric acid with a linear or branched or cyclic alkyl radical or carboxyalkyl radical of a carboxylic acid or aromatic radical.

Examples of such preferred esters are: methyl geranylate, ethyl geranylate, propyl geranylate, butyl geranylate, hexadienylgeranylate, phenylgeranylate, glycylgeranylate, hydroxybutylgeranylate, citrylgeranylate or glycerylgeranylate, and methylcitronellate, ethylcitronitellate, ethyl citronellellate, Phenyl citronellate, glycyl citronellate, hydroxybutyl citronellate, citryl citronellate or glyceryl citronellate.

Preferred compounds according to formulas IV and VI are, for example:

Geranic acid amides, which are derived from geranic acid and various amines, for example also amino acids, according to formulas IV and VI, and citronellic acid amides, which are derived from citronellic acid and various amines, for example also amino acids, according to formulas IV and VI.

Examples of such preferred compounds are: geranic acid amide, N-methylgeranic acid amide, N, N-dimethylgeranic acid amide, N-ethylgeranic acid amide, N, N-diethylgeranic acid amide, N-hydroxyethylgeranic acid amide, N, N-di (hydroxyethyl) geranic acid amide, N-

Ethoxycarbonylgeraniumsäureamid, N, N-Diethoxycarbonyl- geraniumsäureamid and N-methoxycarbonyl-methylgeranium- acid amide and Citronellsäureamid, N-Methylgeraniumsäureamid, N, N-Dimethylcitronellsäureamid, N- Ethylcitronellsäureamid, N, N-Diethylcitronellsäureamid, N- Hydroxyethylcitronellsäureamid, N, N-di ( Hydroxyethyl) citronellamide, N-ethoxycarbonylcitronellamide, N, N-diethoxycarbonylcitronellamide and N-methoxycarbonylmethylcitrone11 acid amide.

Preferred compounds according to formulas V and VII are, for example: hydroxycarboxylic acid amide esters of geranic acid, obtainable by esterifying geranic acid with a hydroxycarboxylic acid amide, and hydroxycarboxylic acid amide esters of citronellic acid, obtainable by esterifying citronellic acid with a hydroxycarboxylic acid amide. Examples of preferred compounds of this type are: glycolamide geranylate, N-hydroxyethylglycolamide geranylate, N-aminoethylglycolamide geranylate, N-methylglycolamide geranylate, N-ethylglycolamide geranylate, N, N-dimethylglycolamide geranylate or N, N-diethylglycolamide geranylate, nitrous glycolate, Methyl glycol amide citronellate, N-ethyl glycol amide citronellate, N, N-dimethyl glycol amide citronellate or N, N-diethyl glycol amide citronellate.

The compounds according to the invention and mixtures thereof are suitable as antimicrobial active ingredients or active ingredient mixtures • for the preservation of microbially perishable preparations and compositions • and / or for the treatment of undesirable microorganisms on or in food or inanimate matter • and / or for the cosmetic or pharmaceutical treatment of dandruff Microorganisms • and / or for cosmetic or pharmaceutical treatment of certain dermatomycosis-causing microorganisms • and / or for cosmetic or pharmaceutical prevention and / or treatment of body odor-causing microorganisms • and / or for cosmetic or pharmaceutical treatment of acne-causing microorganisms.

An essential aspect of the present invention is thus the use of the abovementioned compounds, in particular for combating bacteria, yeasts and / or molds for the simultaneous control of bacteria, yeast and mold.

According to a further embodiment, the invention also relates to the use of derivatives of geranic acid, citronellic acid or geraniol and citronellol (with the exception of geranyl acetate and citronellyl acetate) for combating bacteria, yeasts and / or molds, in particular geranic acid, citronellic acid, perillic acid, geranyl acetate and citronellyl acetate for the simultaneous control of bacteria, yeast and mold.

In particular, an essential aspect of the invention is the use of one or more compounds of the formula II, III, IV, V, VI and / or VII, taking into account the specific activity against gram-negative or gram-positive bacteria and / or yeasts optimized by the derivatization and / or mold. Surprisingly, the derivatization of geranic acid, citronellic acid, geraniol or citronellol can provide new compounds with new, specific effects against gram-positive and / or gram-negative bacteria and / or yeasts and / or molds. Unpredictably, a dependency on the partition coefficient in water / octanol (log Po / w) and thus the hydrophobicity can be determined, in particular with regard to the specific effects of the compounds. In particular, the lipophilic, dandruff-causing yeast Malassezia furfur, the acne-causing bacterium Propionibacteri um acnes and the body odor-causing bacterium Corynebacteri um xerosis become significantly stronger due to the terpenes mentioned in the context of the present invention and derivatives derived therefrom with higher hydrophobicity compared to geraniol or citronellol and correspondingly higher log Po / w, in Particularly inhibited in growth by compounds with a log Po / w value of> 3.59, in particular by perillic acid, geranic acid, citronellic acid, methyl geranylate, ethyl geranylate, methyl citronellate, ethyl citronellate, geranyl succinate and citronelly succinate. The use of perillic acid, geranic acid and / or citric acid to control dandruff-causing microorganisms, especially to combat the dandruff-causing yeast Malassezia furfur, has unexpectedly turned out to be particularly advantageous. The use of perillic acid and / or citronellic acid to combat body odor-causing microorganisms, especially to combat the body odor-causing bacterium Corynebacteri um xerosis, has also unexpectedly proven to be particularly advantageous. Surprisingly, it was also found that carboxylic acid amide esters of geranic acid and citronellic acid, in particular glycolamide pellet and glycolamide citronellate, have a significantly stronger action against molds such as Aspergillus niger and against yeasts such as Candida kefyr.

The invention further relates to the use of one or more compounds from the group consisting of compounds of the formulas I to VII, derivatives of geranic acid, citronellic acid or geraniol and citronellol (except geranyl acetate and citronellyl acetate) for the preparation of compositions for combating bacteria, yeasts and / or molds, in particular geranic acid, citric acid, perillic acid, geranyl acetate and citric acid acetate, for the production of compositions for the simultaneous control of bacteria, yeasts and molds. The use of perillic acid, geranic acid or citronellic acid is used to produce a composition for combating Molds particularly preferred. Another aspect of the invention relates to the use of one or more compounds of the formulas I to VII, optionally in combination with perillic acid, geranic acid, citronellic acid, geranyl acetate and / or citronellyl acetate. In this connection, the compositions may optionally also contain phenoxyethanol in addition to the aforementioned compounds. The antimicrobial effect of phenoxyethanol can thereby be supplemented or enhanced. In particular, em aspect of the invention relates to the use of the compounds of the formulas I to VII, which are also active against molds and yeasts, and perilla acid, geranic acid, citronellic acid, geranyl acetate and / or citronellyl acetate in combination with phenoxyethanol, which has only a slight antimicrobial activity against molds and yeasts Manufacture of compositions for the simultaneous control of bacteria, yeasts and molds. Due to the limited spectrum of activity, phenoxyethanol is usually used in combination with such antimicrobial agents - for example chlorhexide - which have the above-mentioned disadvantages with regard to skin irritation, allergies, cancer or environmental pollution. These disadvantages are avoided by the combinations according to the invention.

A preferred aspect of the present invention is the use of one or more compounds from the group consisting of compounds of the formulas I to VII, perillic acid, geranic acid, citronellic acid, citronellol, geranyl acetate and / or citronellyl acetate for the preparation of compositions for treating dandruff-causing microorganisms and of Perillic acid, geranic acid, citric acid, geraniol, geranyl acetate and / or citric acid acetate for the preparation of compositions for Treatment of acne-causing microorganisms or the use of one or more compounds from the group consisting of compounds of the formulas I to VII, perillic acid, citric acid, geranyl acetate and / or citric acid acetate for the preparation of compositions for the treatment of body odor-causing microorganisms or the use of one or several compounds from the group consisting of compounds of the formulas I to VII, perillic acid, citronellic acid, citronellol and / or citronellyl acetate for the preparation of compositions for the treatment of dermatomycosis-causing microorganisms.

According to the invention, the composition can be an agent for the preservation of cosmetic, dermatological or pharmaceutical preparations.

The composition can generally be a means of preserving water-containing preparations.

The composition is preferably an ointment, a cream, a hydrogel, an emulsion, a lotion, a paste, a tincture, a shampoo, a pump spray, a toothpaste, a cleansing milk, a soap, a mouthwash or a juice.

In another embodiment, the composition is a food preservative.

Also included in the present invention is a composition that is a means of preserving fruits, vegetables, and live animals.

A use in which the living animals are lobsters, mussels or oysters is particularly preferred. Another preferred aspect is a use in which the composition is an agent for treating casings,

Skinning or peeling cheese or sausages is all about that

Prevent the growth of bacteria, yeast and / or mold, which affect the edibility, shelf life and harmlessness to health.

According to a further embodiment, the invention relates to the use for the production of a crop protection agent.

The composition is particularly preferably a pharmaceutical preparation.

According to a further use, the composition is a means of preserving technical preparations such as paints, varnishes, wood preservatives, glues or a component of wall mold removal preparations which is effective against wall mold.

For the uses mentioned, it is particularly advantageous if the compound or compounds from the group consisting of compounds of the formulas I to VII, perillic acid, geranic acid, citronellic acid, geraniol and citronellol, citronellyl acetate and / or geranyl acetate in a total concentration of 0.001 to 10% by weight, in particular 0.1 to 2% by weight, is / are present in the preparation.

A particular advantage of the use according to the invention of compounds of the formula I to VII, of perillic acid, geranic acid, citronellic acid, geraniol, citronellol, citronellyl acetate and / or geranyl acetate is that the use of conventional, but in particular several different preservatives can be dispensed with, since for the above-mentioned active substances in the context of the present invention, both antibacterial activity and activity against yeasts and molds have been demonstrated. Especially with regard to the critical consumer of cosmetics, for example, it is a further advantage that perillic acid, geranic acid, citronellic acid, geraniol and citronellol are naturally occurring compounds.

Cosmetic, dermatological or pharmaceutical preparations, food or pesticides as well as technical preparations such as paints, varnishes, wood preservatives or wall mold removers which contain one or more compounds of the formulas I to VII and, if appropriate, additionally perillic acid, geranic acid, citronellic acid, geraniol, citronellol, citronelly acetate and / or contain Gernay acetate form a further aspect of the invention.

Preferred cosmetic, dermatological or pharmaceutical preparations, foods, crop protection agents or technical preparations are those which contain the compound or compounds from the group consisting of compounds of the formulas I to VII, perillic acid, geranic acid, citronellic acid, geraniol, citronellol, citronelly acetate and / or Gernay acetate in a total concentration of 0.001 to 10% by weight, preferably 0.1 to 2% by weight.

Processes for the preparation of compounds according to formula II, in which geraniol or citronellol are chemically or enzymatically acylated with organic acids or fatty acids or their halides or anhydrides, form a further part of the present invention. The present invention likewise relates to processes for the preparation of compounds of the formulas III, IV, V, VI and VII, in which geranic acid or citronellic acid is esterified chemically or enzymatically with alcohols or hydroxylated carboxylic acids or geranic acid or citronellic acid is amidated with amines or amino acids or geranic acid or Citronellic acid esterified with a chlorocarboxamide. For N-substituted chlorocarboxamides, the process is modified in such a way that the amide function of a compound of the formula III in which R ^{4 is} an alkenyl radical such as propenyl, 2-butenyl, 3-butenyl, 3-pentenyl or 1,3-hexadienyl, or an alkynyl radical, such as propynyl, 2-butynyl, 3-butynyl, 4-hexynyl or 1-decynyl, is converted into the corresponding carboxylic acid by base-catalyzed hydrolysis and subsequently converted into the corresponding carboxylic acid chloride by halogenating agents, which is then substituted with an appropriate N-substituted one Amine is implemented.

The invention is explained below using examples.

Examples

Example 1:

Preparation of glycolamide geranylate

3.06 g of geranic acid were dissolved in 50 ml of ethyl acetate, and 5.75 ml of triethylamine, 571 mg of sodium iodide and 3.84 g of 2-chloroacetamide were added. The mixture was refluxed for 6 hours. After the mixture had cooled, it was filtered and the filtrate was washed twice with 2% sodium thiosulfate solution, 2% sodium hydrogen carbonate solution and water, dried over sodium sulfate and the ethyl acetate was stripped off. The residue (3.23 g) was the clean product. The yield of glycolamide geranylate was 80%.

Example 2:

HPLC analysis of glycolamide geranylate

The HPLC analysis of the glycolamide geranylate was carried out under the following running conditions: LiChrospher RP-8 column; 40 ° C; 1 ml / min; Eluent: 20% water, 32% ammonium acetate (pH 5), 48% methanol in a gradient to 100% methanol; λ = 220 nm

Example 3:

Preparation of N, N-diethylglycolamide geranylate

3.06 g of geranic acid were dissolved in 50 ml of ethyl acetate, and 5.75 ml of triethylamine, 571 mg of sodium iodide and 6.14 g of N, N-diethyl-2-chloroacetamide were added. The mixture was refluxed for 6 hours. After the mixture had cooled, it was filtered and the filtrate was washed twice with 2% sodium thiosulfate solution, 2% sodium hydrogen carbonate solution and water, and dried over sodium sulfate and stripped off the ethyl acetate. The residue (5.59 g) was the clean product. The yield of N, N-diethylglycolamide geranylate was 85%.

Example 4:

HPLC analysis of the N, N-diethylglycolamide qeranylate

The HPLC analysis of the N, N-diethylglycolamide geranylate was carried out under the following running conditions: LiChrospher RP-8 column; 40 ° C; 1 ml / min; Eluent: 20% water, 32% ammonium acetate (pH 5), 48% methanol in a gradient to 100% methanol; λ = 220 nm

Example 5: Preparation of methyl qeranylate

1 g of geranic acid was dissolved in 20 ml of dichloromethane, treated with 1.75 ml (2.86 g) of thionyl chloride and heated under reflux for 2 h. The solvent and excess thionyl chloride were then distilled off. The residue was suspended in 10 ml of methanol and stirred at room temperature (20 ° C.) overnight. The methanol was then distilled off. The remaining oily liquid was the pure product. The yield of methyl geranylate (1.02 g) was 93%.

Example 6:

HPLC analysis of methyl qeranylate

The HPLC analysis of the methyl geramylate was carried out under the following running conditions: LiChrospher RP-8 column; 40 ° C; 1 ml / min; Eluent: 40% ammonium acetate (pH 5), 60% methanol; λ = 220 nm.

Example 7: Preparation of ethyl qeranylate (enzymatic)

82 mg (0.5 mmol) of geranic acid were suspended in 5 ml of t-butanol in a 25 ml Schlenk tube. 29 μl (0.5 mmol) of ethanol and 100 mg of lipase (Candida antarctica, Novozym® 435) were then added in a stream of nitrogen. The mixture was stirred at 60 ° C. for 144 hours. To control the reaction, 10 μl samples were taken continuously during the reaction and these were analyzed chromatographically (HPLC). After the reaction was stopped, the solvent was stripped off and the reaction mixture was separated by chromatography. 19.6 mg of ethyl geranylate were obtained, the yield was 20%.

Example 8 HPLC analysis of ethyl geranylate

The HPLC analysis of the ethyl geranylate was carried out under the following running conditions: LiChrospher RP-8 column; 40 ° C; 1 ml / min; Eluent: 40% ammonium acetate (pH 5), 60% methanol; λ = 220 nm. In game 9

Chromatographic purification of ethyl geranylate

The chromatographic purification of ethyl geranylate was carried out on a preparative RP phase (C18; ODS-AQ) under the following running conditions: RT, 5 ml / min; Eluent: 40% ammonium acetate (pH 5), 60% methanol, λ = 220 nm.

Example 10: Preparation of geranyl succinate

100 mg of succinic anhydride were dissolved in 79 ml of DMAP in 10 ml of dichloromethane, 80 μl of geraniol were added and the mixture was stirred at room temperature for 16 hours. The mixture was washed with 0.5 N hydrochloric acid and then with water, dried over sodium sulfate and the dichloromethane was distilled off. 104.7 mg of geranyl succinate remained, the yield was 90%.

Example 11:

HPLC analysis of geranyl succinate

The HPLC analysis of the geranyl succinate was carried out under the following running conditions: LiChrospher RP-8 column; 40 ° C; 1 ml / min; Eluent: 60% methanol: 40% water in a gradient to 100% MeOH; λ = 210 nm.

Example 12:

Determination of hydrophobicity

To determine the hydrophobicity, which provides information about the water solubility of a compound, the partition coefficient in water / octanol (log Po / w) was determined using the Interactive LogKow program (SRC ^'s KowWin Program), based on the publication by Meylan and Howard (J. Pharm. Sei. 84 (1995) 83-92).

The larger a log Po / w, the more parts of the compound dissolve in octanol, the smaller the log Po / w, the more parts dissolve in water. A large log Po / w indicates a more hydrophobic, a small log Po / w indicates a more hydrophilic and therefore more water-soluble compound.

The following log Po / w values were determined:

Connection log Po / w

Geranic acid 3.70

Citronellic acid 3.78

Glycolamide geranylate 2.41

N, N -diethylglycolamide geranylate 4.22

Methyl geranylate 3.98

Ethyl geranylate 4.48

Geraniol 3.47

Citronellol 3.56

Geranyl malate 3.81

Geranyl succinate 4.25

Perillic acid 3.59

Citral 3.45

Lime 4.83

Linalool 3.38

Example 13:

Determination of the antimicrobial effect in the agar diffusion test (disc agar diffusion assay)

This assay was used to test the growth inhibition of gram-negative and gram-positive bacteria, yeasts and molds.

In the agar diffusion test, growth-free zones of inhibition result from the diffusion of an antimicrobial agent from a filter sheet into a solid, inoculated medium. The size of the zone of inhibition depends on the antimicrobial effect. The testing was carried out on a reference medium standardized according to DIN 58940, the Müller-Hinton agar. The Testing against Propionibacteri um acnes was carried out on anaerobic cooking meat medium (medium 78, DSMZ). Malassezia furfur was tested on Pityrosporum medium (Medium 472, DSMZ). Petri dishes with a diameter of 9 cm were used, into which 20 +/- 1 ml of medium were filled.

The following test strains (at the indicated incubation temperature) were used: Bacill us subtilis DSM 347 (gram ^¬ positive; 30 ° C), Micrococcus l uteus DSM 1790 (Gram-positive; 30 ° C), Escherichia coli DSM 498 (gram-negative; 37 ° C), Pseudomonas aeruginosa DSM 1117 (gram-negative; 37 ° C), Candida kefyr DSM 70073 (yeast; 30 ° C), Aspergill us niger DSM 1988 (mold; 30 ° C).

The yeast Malassezia furfur DSM 6171 (30 ° C.) was used to test the antimicrobial activity against dandruff-causing microorganisms.

The yeast Candida albicans was used to test the antimicrobial activity against microorganisms causing dermatomycoses

DSM 1665 (30 ° C) was used. The gram-positive, coryneform bacterium Corynebacterium xerosis DSM 20743 was used to test the antimicrobial activity against body odors

(37 ° C) used.

The gram-positive, anaerobic, coryneform bacterium Propionibacteri by acnes DSM was used to test the antimicrobial activity against acne-causing microorganisms

Used in 1897 (37 ° C). The following compounds were tested for their antimicrobial activity:

Geranium acid, citric acid, perilla acid, glycolamide geranylate, N, N-diethylglycolamide geranylate,

Methyl geranylate, ethyl geranylate, geraniol, citronellol, geranyl succinate, citral.

The following substances used as preservatives in the cosmetics industry were used as reference substances:

Phenylethanol, R-limonene, linalool.

The bacteria and yeasts were applied to the agar plates as a preculture with a defined number of cells and plated out. Per plate approximately 5 x 10 ⁵ CFUs (colony forming units ^~) were abandoned. A sufficient amount of a stock culture plate was removed from the Aspergillus niger and plated out. After the inoculated plates had dried, filter sheets (cellulose, grade 740e, Schleicher &Schull; diameter 6 mm) were applied with slight pressure.

The test substances are dissolved as a 5% solution in dimethyl sulfoxide (with 0.1% Tween 20) and 10 .mu.l in each case are dropped on a filter pad. After a subsequent incubation (24 h), the diameters of the growth-free, clear zones of inhibition were measured. The results are shown in Tables 1 and 2: Table 1: Results of the agar diffusion test (diameter of the inhibition zones in mm)

10 μl of a 5% active ingredient solution of dimethyl sulfoxide (with 0.1% Tween 20) were used in each case. The incubation was carried out for 24 hours. Organisms Bacill US Micrococcus Escherichia Pse domonas Candida Aspergill us subtle isl uteus coli aeruginosa kefyr niger Active ingredient Geranic acid 18 16 11 9 20 11 Citronellic acid 21 15 12 11 22 11 Perillic acid 14 13 11 9 20 14 Glycolamide geranylate 20 16 12 10 25 20 N, N- Diethyl glycol 18 10 10 9 18 14 amidgeranylate methyl geranylate 12 10 8 6 13 11 ethyl geranylate 11 10 8 6 12 10 geraniol 17 14 8 8 17 9 citronellol 16 12 10 8 17 10 geranyl succinate 14 11 8 9 14 9 citral 18 14 9 7 18 8 Reference: R-Limonen 7 7 9 6 9 6 Reference: Linalool 9 8 9 7 9 6 Reference:

Phenylethanol 10 10 9 7 8 6

Table 2: Results of the agar diffusion test (diameter of the inhibition zones in mm) 10 μl of a 5% active ingredient solution in dimethyl sulfoxide (with 0, Tween 20) were used in each case. The incubation was carried out for 24 hours. Organi smen Propi onibacteri um Cory-nejbacteri um Malassezia furfur Candida albi cans acnes xerosis active ingredient geranic acid 11 14 22 18 citronellic acid 11 20 22 21 perillic acid 11 18 20 18 glycolamide geranylate 9 11 12 24 N, N-diethyl-glycol-11 18 20 18 amidgeranylate Methyl geranylate 12 16 16 14 ethyl geranylate 13 16 18 13 geraniol 9 14 12 16 citronellol 9 13 12 17 geranyl succinate 12 17 20 14 citral 9 14 16 18 reference: R-limonene 6 6 6 9 reference: linalool 6 7 6 9 reference: phenylethanol 6 6 7 8

Example 14: Determination of the minimum inhibitory concentration (MIC)

The macrodilution method with a total volume of 2 ml of medium was used. Malassezia furfur was tested in Pityrosporum medium, Propionibacteri um acnes in cooking meat broth and all other microorganisms in Müller-Hinton broth. To determine the MIC, a series of test tubes with defined organism inoculum (1 X 10 ⁵ CFU / ml), the same volume of Müller-Hinton broth (1.98 ml) and the same volume of differently concentrated drug solutions (20 μl) were used. filled. The minimum inhibitory concentration (MIC) represents the lowest

Concentration (in%) of an active ingredient that prevents the in-vitro growth of bacteria or yeast within the specified period of 48 hours.

The multiplication of the microorganisms was determined photometrically by measuring the optical density at 600 nm (OD ₆₀ o). The MIC corresponds to the concentration of the active ingredient, in which no increase in OD ₆ oo after 48 h of incubation was determined.

The following test strains (and incubation temperatures) were used:

Bacillus subtilis DSM 347 (gram-positive; 30 ° C), Micrococcus luteus DSM 1790 (gram-positive; 30 ° C), Escheri chia coli DSM 498 (gram-negative; 37 ° C), Candida kefyr DSM 70073 (yeast; 30 ° C);

Malassezia furfur DSM 6171 (dandruff yeast, 30 ° C);

Candida albicans DSM 1665 (dermatomycosis-causing yeast, 30 ° C); Propionibacteri um acnes DSM 1897 (acne causing, gram positive, 37 ° C);

Corynebacteri um xerosis DSM 20743 (body odor, gream positive, 37 ° C). Molds cannot be cultivated under the conditions of this method.

The following compounds were tested for their antimicrobial activity:

Geranium acid, citric acid, perilla acid,

Glycolamide geranylate, N, N-diethylglycolamide geranylate,

Phenylethanol, R-limonene.

The following active ingredient concentrations (in a 2 ml batch) were used:

0.01% to 0.1% (in 0.005% steps) and 0.1% to 0.5% (in 0.05% steps)

Table 3: Results of the macrodilution tests to determine the minimum inhibitory concentration (MIC). The active substance concentration is shown (in% v / v, based on 2 ml total volume) at which no increase in OD ₆ oo was found after 48 h of incubation. In each case 20 μl of an active ingredient solution in dimethyl sulfoxide (with 0.1% Tween 20) were used. The incubation was 48 h. The test was carried out in 1.98 ml of medium.

Organisms Bacillus Micrococcus E. coli Candida subtilis luteus kefyr

Active ingredient MHK (v / v)

Geranic acid 0.05% 0.1% 0.1% 0.02%

Citric acid 0.05% 0.08% 0.08% 0.015%

Perillic acid 0.06% 0.08% 0.1% 0.02%

Glycolamide geranylate 0.03% 0.06% 0.05% 0.01%

N, N-Diethylglycol- 0.08% 0.08% 0.1% 0.03% amidgeranylate ethylgeranylate 0.1% 0.15% 0.15% 0.075%

Ethyl geranylate 0.15% 0.2% 0.15% 0.15%

Geraniol 0.08% 0.15% 0.1% 0.1%

Citronellol 0.1% 0.15% 0.15% 0.1%

Geranyl succinate 0.1% 0.2% 0.2% 0.2%

Citral 0.08% 0.15% 0.15% 0.15%

Reference:

R-Limonene> 0.5%> 0.5%> 0.5%> 0.5%

Reference:

Linalool 0.3% 0.4%> 0.5% 0.3%

Reference:

Phenylethanol>0.5%>0.5%>0.5%> 0.5%

Table 4 Results of the macrodilution tests to determine the minimum inhibitory concentration (MIC). The active substance concentration is shown (in% v / v, based on 2 ml total volume) at which no increase in OD _δ oo was found after 48 h of incubation. In each case 20 μl of an active ingredient solution in dimethyl sulfoxide (with 0.1% Tween 20) were used. The incubation was 48 h. The test was carried out in 1.98 ml medium.

Organisms propionib. Cory-πejact. Candida malassezia acnes xerosis albicans furfur

Active ingredient MIC (v / v)

Geranic acid 0.15% 0.08% 0.025% 0.02%

Citric acid 0.1% 0.05% 0.02% 0.015%

Perillic acid 0.2% 0.1% 0.025% 0.02%

Glycolamide geranylate 0.1% 0.15% 0.02% 0.1%

N, N-diethylglycol 0.15% 0.1% 0.08% 0.06% amide geranylate

Methyl geranylate 0.2% 0.1% 0.075% 0.08%

Ethyl geranylate 0.3% 0.1% 0.05% 0.06%

Geraniol 0.18% 0.3% 0.1% 0.3%

Citronellol 0.16% 0.25% 0.15% 0.25%

Geranyl succinate 0.2% 0.08% 0.2% 0.1%

Citral 0.12% 0.2% 0.25% 0.25%

Reference:

R-Limonene> 0.5%> 0.5%> 0.5%> 0.5%

Reference:

Linalool> 0.5%> 0.5%> 0.5%> 0.5%

Reference:

Phenylethanol> 0.5%> 0.5%> 0.5%> 0.5%

Example 15:

Preparation of formulations which contain the compounds according to the invention as antimicrobial substances

The following formulations were made with perillic acid,

Geraniumsäure, Hydroxycarbonsäureamidestern the

Geranic acid, amides of geranic acid, esters of

Geranic acid, geraniol or esters of geraniol,

Citronellic acid, Hydroxycarbonsäureamidestern der

Citronellic acid, amides of citronellic acid, esters of citronellic acid, citronellolol or esters of citronellol are prepared. In the following, the term "geranium compound" is used for all of the substances mentioned The term "formulations" is used here as a synonym for the term "preparations".

In the formulations, the compounds can serve, for example, as preservatives or as active substances against certain bacteria, yeasts or molds. If the formulations are mixed with the compounds according to the invention, the substances can kill bacteria, yeasts or mold or prevent their growth.

The following formulations represent only a few examples of preferred embodiments according to the invention. Numerous modifications of these examples can be made, and consequently all these modifications are to be included in accordance with the scope and essence of the invention.

Chemical q. Ge -s. -Gew de: r formulation X a.) Preserved oil vegetable oil 99-99, 99 geranium compound 0, 01-1 b.) Ethanolic solution ethanol 99-99, 99 geranium compound 0, 01-1 c.) Water / Oil cream Vaseline 2 -5 paraffin oil (DAB 9) 10 wool wax alcohol 1 glycerin 1 -3 vegetable. Oils 1 -5 active ingredients 0, 1-10 perfume 0, 1-2 geranium compound 0, 01-1 water ad 100

d.) Water in Oil Lotion Paraffin Oil (DAB 9) 20 Vaseline 2-5 Stearate / Palmitate 1-3 Glycerin 1-5 Emulsifiers 1-3 Active Agents 0.1-10 Perfume 0.1-2 geranium compound 0.01-1 water ad 100 e. ) Oil in water lotion paraffin oil (DAB 9) 10 petroleum jelly 2-5 stearates / palmitates 2-5 glycerin 1-5 emulsifiers 1-3 active ingredients 0.1-10 perfume 0.1-2 geranium compound 0.01-1 water ad 100

Oil in water vegetable oil 10-15 emulsion emulsifier 1-3 tween 40 2-4 geranium compound 0.01-1 water ad 100 g. ) Shampoo water> 50 lauryl compounds 10-20 glycerin 0 -, - ll wash-active substances 0.2-5 perfume 0.1-1 ethanol 0.1-1 citric acid 0.1-1 plant extracts 0.05-2 geranium Compound 0.01-1 h. ) Hair tonic isopropanol 25-35 plant extracts 0.05-2 perfume 0.1-1 geranium compound 0.01-1 water> 50

1. mouthwash ethanol 98-99.89 flavor 0, 1-1 geranium compound 0.01-2 j. ) Deodorant pump spray ethanol 30-65 emulsifier 1-5% citric acid 0.02 geranium compound 0.05-2 water> 30

Claims

claims

Use of a compound of general formula I.

I,

where XZ is CH-CH ₂ or C = CH and where R CR ¹ R ² 0 (CO) R ³ , COOR ⁴ , CONR ⁵ R ^δ , COO (CH ₂ ) _n CONR ⁷ R ⁸ ,

COR ⁹ or COO (CH ₂ ) _n COR ¹⁰ , where

R ¹ and R ^{2 are} each independently hydrogen or a linear or branched alkanyl radical,

R ^{3 is} hydrogen or a linear or branched alkanyl radical with a chain length of 1 or 3 to 8 carbon atoms from the group consisting of methyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, a linear or branched alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl, citronellyl, geranyl, a linear or branched alkynyl radical from the group consisting of propynyl, 2-butynyl, 3-butynyl, 2-pentynyl, or the radical of a branched or straight-chain ^¬, saturated or unsaturated polycarboxylic acid having a length of 2 to 5 carbon atoms from the group consisting of oxalic acid, ethyl oxalic acid, malonic acid, succinic acid, glutaric acid or the remainder of a hydroxy acid with a length of 2 to 5 carbon atoms from the group consisting of glycolic acid, lactic acid, malic acid, hydroxybutyric acid, glyceric acid, hydroxypropionic acid, citric acid, isoic acid, or citric acid, or citric acid or the residue of an amino acid from the group consisting of alanine, glycine or glutamine,

R ^{4 is} a linear or branched alkanyl radical with a chain length of 1 to 8 carbon atoms from the group consisting of methyl, ethyl, hydroxyethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl, citronellyl, geranyl, alkynyl radical from the group consisting of propynyl, 2-butynyl, 3-butynyl, 2-pentynyl, or the residue of a branched or unbranched, saturated or unsaturated mono- or polycarboxylic acid which is hydroxylated to one to five times, the carboxylic acid being selected from the group consisting of glycolic acid, lactic acid, malic acid, hydroxybutyric acid, glyceric acid , Hydroxypropionic acid, citric acid, isocitric acid is selected,

R ⁵ and R ^{6 are} each independently hydrogen, a linear or branched alkanyl, alkenyl, or alkynyl radical with a chain length of 1 to 8 carbon atoms, the alkanyl radical being selected from the group consisting of methyl, ethyl , Hydroxyethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, the alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl and the Alkynyl radical is selected from the group consisting of propynyl, 2-butynyl, 3-butynyl, 2-pentynyl,

n is an integer from 1 to 22 and

R ⁷ and R ⁸ independently of one another are hydrogen, a linear or branched alkanyl, alkenyl or alkynyl radical with a chain length of 1 to 5 carbon atoms, the alkanyl radical being selected from the group consisting of methyl, ethyl, hydroxyethyl, Propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, the alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl and the alkynyl radical from the group consisting of propynyl, 2-butynyl, 3- Butynyl, 2-pentynyl is selected,

R ⁹ and R ^{10 are} each the residue of an amino acid,

and / or a salt thereof,

for the preparation of compositions

to fight bacteria, yeast and / or mold,

for the treatment of dandruff-causing microorganisms,

for the treatment of dermatomycosis-causing microorganisms,

for the treatment of body odor causing microorganisms or for the treatment of acne-causing microorganisms.

2. Use according to claim 1, wherein R CR ¹ (R ² ) 0 (CO) R ³ , wherein the compound has the general formula II

II or a salt thereof, where XZ has the above meaning, R ¹ and R ^{2 have} the above meaning and

R ^{3 is} hydrogen or a linear or branched alkanyl radical with a chain length of 1 or 3 to 8 carbon atoms from the group consisting of methyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, or a linear or branched alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl, citronellyl, geranyl, or a linear or branched alkynyl radical the group consisting of propynyl, 2-butynyl, 3-butynyl, 2-pentynyl, or the remainder of a branched or unbranched, saturated or unsaturated polycarboxylic acid with a length of 2 to 5 carbon atoms from the group consisting of oxalic acid, ethyl oxalic acid, malonic acid , Succinic acid, glutaric acid or the rest of a hydroxy acid with a length of 2 to 5 carbon atoms from the group consisting of glycolic acid, lactic acid, Malic acid, hydroxybutyric acid, glyceric acid, hydroxypropionic acid, citric acid, isocitric acid or tartaric acid, or the rest of an amino acid from the group consisting of alanine, glycine or glutamine.

3. Use according to claim 1, wherein R is COOR ⁴ , wherein the compound has the general formula III

III or a salt thereof, wherein

X-Z has the above meaning and

R ^{4 is} a linear or branched alkanyl radical with a chain length of 1 to 8 carbon atoms from the group consisting of methyl, ethyl, hydroxyethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, a linear or branched alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl, citronellyl, geranyl, a linear or branched alkynyl radical from the group consisting of propynyl, 2-butynyl, 3-butynyl, 2-pentynyl, or the remainder of a branched or unbranched, saturated or unsaturated mono- or polycarboxylic acid which is hydroxylated one to five times, the carboxylic acid being selected from the group consisting of glycolic acid , Lactic acid, malic acid, hydroxybutyric acid, glyceric acid, hydroxypropionic acid, citric acid, isocitric acid is selected. Use according to claim 1, wherein R is CONR ⁵ R ⁵ , the compound having the general formula IV

IV

or is a salt thereof, wherein

X-Z has the above meaning and

R ⁵ . and R ⁶ is, independently of one another, hydrogen, a linear or branched alkanyl, alkenyl or alkynyl radical with a chain length of 1 to 8 carbon atoms, the alkanyl radical being selected from the group consisting of methyl, ethyl , Hydroxyethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, the alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl and the alkynyl radical from the group consisting of propynyl, 2-butynyl, 3- Butynyl, 2-pentynyl is selected.

Use according to claim 1, wherein R is COO (CH ₂ ) _n CONR ⁷ R ⁸ , the compound having the general formula V

v

or is a salt thereof, wherein

X-X has the meaning given above,

n is an integer from 1 to 22 and

R and R independently of one another are hydrogen, a linear or branched alkanyl, alkenyl or alkynyl radical with a chain length of 1 to 5 carbon atoms, the alkanyl radical being selected from the group consisting of methyl, ethyl, hydroxyethyl, propyl, Isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, the alkenyl radical from the group consisting of 2-propenyl, 2-butenyl, 3-butenyl, 3-pentenyl and the alkynyl radical from the group consisting of propynyl, 2-butynyl, 3- Butynyl, 2-pentynyl is selected. Use according to claim 1, wherein R is COR ⁹ , wherein the compound has the general formula VI

VI or a salt thereof, wherein

X-Z has the above meaning,

R is the residue of an amino acid which is bonded to the carbonyl carbon atom via its NH ₂ group, the amino acid being selected from the group consisting of glycine, alanine, cysteine, serine, threonine, lysine, glutamic acid and aspartic acid.

7. Use according to claim 1, in which R is COO (CH ₂ ) _n COR, 10, the compound having the general formula VII

0

VII or a salt thereof, wherein

XZ has the above meaning n is an integer from 1 to 22 and

R ^{10 is} the residue of an amino acid which is bonded to the carbonyl carbon atom via its NH ₂ group, the amino acid being selected from the group consisting of glycine, alanine, cysteine, serine, threonine, lysine, glutamic acid and aspartic acid.

8. Use of perillic acid, geranic acid, citronellic acid, citronelly acetate, geranyl acetate and / or according to one of claims 1 to 7 for the simultaneous control of bacteria, yeasts and molds.

9. Use of perillic acid, geranic acid, citronellic acid, citronelly acetate, ^" geranyl acetate and / or according to one of claims 1 to 7 in combination with phenoxyethanol for the simultaneous control of bacteria, yeasts and molds.

10. Use of perillic acid, geranic acid, citronellic acid, citronellol, citronellyl acetate and / or geranyl acetate for the production of compositions for the treatment of dandruff-causing microorganisms.

11. Use of perillic acid, citronellic acid, citronellol, and / or citronelly acetate for the preparation of compositions for the treatment of dermatomycosis-causing microorganisms.

12. Use of perillic acid, citric acid, citric acid acetate and / or geranyl acetate for the preparation of compositions for the treatment of body odor-causing microorganisms.

13. Use of perillic acid, geranic acid, citronellic acid, geraniol, citronelly acetate and / or geranyl acetate for the preparation of compositions for the treatment of acne-causing microorganisms.

That the composition is 14. Use according to claims 1 to 13, characterized in that a means of cosmetic, dermatological or phar ^¬ for preserving mazeutischer preparations.

15_. Use according to claims 1 to 13, characterized in that the composition ^"is a means of preserving water-containing preparations.

16. Use according to claims 14 and 15, characterized in that the composition is an ointment, a cream, a hydrogel, an emulsion, a lotion, a paste, a tincture, a shampoo, a pump spray, a toothpaste, a cleansing milk, a Soap, mouthwash or juice.

17. Use according to claims 10 to 13, characterized in that the composition is an ointment, a cream, a hydrogel, an emulsion, a lotion, a paste, a tincture, a shampoo, a pump spray, a cleaning milk or a soap.

18. Use according to claims 1 to 13, characterized in that the composition is a means of preserving food.

19. Use according to claim 18, characterized in that the composition is a means of preserving fruit, vegetables and live animals.

20. Use according to claim 19, wherein the live animals are lobsters, mussels or oysters.

21. Use according to claim 18, characterized in that the composition is an agent for the treatment of casings, skins or skins of cheese or sausage products in order to prevent the growth of bacteria, yeasts and / or molds, which reduce the edibility, durability and health Impair safety.

22. Use according to claims 1 to 13, characterized in that the composition comprises a plant ^¬ retardant is.

23. Use according to claims 1 to 13, characterized in that the composition is a means for preserving technical preparations, paints, varnishes, wood preservatives, glues and / or a component of wall mold removal preparations effective against wall mold.

24. Use according to one of claims 8 to 23, characterized in that in the composition the compound or compounds from the group consisting of those mentioned in claims 1 to 7 Compounds, perillic acid, geranic acid, citronellic acid, geraniol, citronellol, citronelly acetate and / or geranyl acetate are / are contained in a total concentration of 0.001 to 10% by weight.

25. Use according to claim 24, characterized in that the concentration is 0.1 to 2% by weight.

26. Cosmetic, dermatological or pharmaceutical preparation, characterized in that it contains one or more of the compounds mentioned in claims 1 to 7.

27. Cosmetic, dermatological or pharmaceutical preparation according to claim 26, characterized in that it further contains perillic acid, geranic acid, citronellic acid, geraniol, citronellol, citronelly acetate ^" and / or geranyl acetate.

28. Food, pesticides or preservatives for technical preparations, characterized in that there are one or more compounds from the group consisting of compounds which are mentioned in claims 1 to 7, perillic acid, geranic acid, citronellic acid, geraniol, citronellol, citronellyl acetate and / or contains geranyl acetate.

29. A preparation, food, crop protection agent or preservative for industrial preparations according to any one of claims 26 to 28, characterized in that it is the compound or compounds from the group consisting of compounds mentioned in claims 1 to 7, perillic acid, geranic acid . Contains citronellic acid, geraniol, citronellol, citronelly acetate and / or geranyl acetate in a total concentration of 0.001 to 10% by weight.

30. preparation, food, pesticides or preservatives for technical preparations according to claim 29, characterized in that the concentration is 0.1 to 2 wt.%.