DE102009029630A1 - Antimicrobial amides - Google Patents

Abstract

The invention relates to the use of certain amides for reducing the growth of microorganisms and formulations comprising these amides.

Description

Field of the invention

The invention relates to the use of certain amides for reducing the growth of microorganisms and formulations comprising these amides.

Antimicrobial agents are widely used in cosmetic deodorants or antiperspirants, anti-dandruff and anti-acne formulations, foot care and intimate hygiene products, as well as oral hygiene and dental care products.

Body odor arises especially when the initially odorless sweat is decomposed by microorganisms on the skin. Only the microbial decomposition products cause the unpleasant smell of sweat. This arises especially where there is a high density of sweat glands and also has a high density of odoriferous germs, such. B. under the armpits in the genital area or on the feet. The responsible for this germs are common but not exclusively to the genus Corynebacterium.

Our natural skin flora includes many different bacteria, including staphylococci, certain streptococci, occasionally enterococci, corynebacteria and propionibacteria. They live on the skin, partly in the pores, in sweat glands and passages as well as in the oral cavity. Likewise, various fungi are found on the skin.

Certain skin diseases are also associated with excessive growth of unwanted microorganisms on the skin. For example, acne is caused by uncontrolled proliferation of the anaerobic skin bacterium Propionibacterium acnes. Candida albicans is responsible for the formation of thrush, dandruff may become. a. in connection with the fungus Malassezia furfur.

In the field of oral hygiene play microorganisms, eg. As in the development of tooth decay and plaque, an essential role. The most important causative agent of dental caries is, for example, Streptococcus mutans.

Furthermore, antimicrobial agents are used in private, industrial and institutional areas, for example in the area and device disinfection and cleaning. Especially in the private sector has become more and more conscious of a hygienic clean environment enforced This is achieved for example by the addition of antimicrobial agents in cleaning and care products in Tränklosungen but also by the direct coating of surfaces, such as waste bags, with the antimicrobial agents.

State of the art

wobei RCO ein Fettsäurerest, X -CHR₁CH₂OH, wobei R₁ -H oder niederer Alkylrest und Y -H, Alkyl, Alkanol oder -CHR₁CH₂OH als Bestandteil eines Klarheitsverbesserers in klaren Deosticks. Eine antimikrobielle Wirkung wird den Verbindungen nicht zugeschrieben. US 5,407,668 describes compounds of the general structure

where RCO is a fatty acid radical, X is -CHR ₁ CH ₂ OH, where R _{1 is} -H or lower alkyl radical and Y is -H, alkyl, alkanol or -CHR ₁ CH ₂ OH as a constituent of a clarity enhancer in clear deosticks. An antimicrobial effect is not attributed to the compounds.

wobei R³ CH₃-(CH₂)₅- oder CH₂=CH-(CH₂)₈- und R¹, R² H oder gegebenenfalls hydrophil substituierter C1 bis C20 Alkylrest, wobei diese Heptansäure (C7) und Undecylensäure (C11:1)-Amide als bakteriostatische Wirkstoffe in Metallbearbeitungsfluiden eingesetzt werden. Außerdem beschreibt die DE 24 32 882 Haarpflegeprodukte enthaltend Pelargonsäure(C9)-Amide als antimikrobielle Wirkstoffe zur Behandlung von Schuppen, so wie die JP 2000191511 Feuchttücher enthaltend Undecylensäureethanolamid als antibakteriellen Wirkstoff.The antimicrobial effect of amides of the odd-numbered carboxylic acids, in particular of the C7, C9, C11 and C11: 1 carboxylic acids is known, for example described WO 9635767 Compounds of the general structure

wherein R ^{3 is} CH ₃ - (CH ₂ ) ₅ - or CH ₂ = CH- (CH ₂ ) ₈ - and R ¹ , R ² H or optionally hydrophilically substituted C1 to C20 alkyl radical, said heptanoic acid (C7) and undecylenic acid (C11 : 1) -amides as bacteriostatic Active ingredients are used in metalworking fluids. In addition, the describes DE 24 32 882 Hair care products containing Pelargonsäure (C9) -amides as antimicrobial agents for the treatment of dandruff, such as JP 2000191511 Wet wipes containing undecylenic acid ethanolamide as an antibacterial agent.

In particular, the antimicrobial effect of the amides of undecylenic acid is in the writings US 3385755 . GB 2354771 and JP 2001214368 described.

The availability of the odd-numbered carboxylic acids is limited and the extraction of natural raw material sources, as desired for the production of ingredients for cosmetics, is associated with high costs.

The object of the invention was therefore to provide compounds which effect the reduction of the growth of microorganisms, in particular on a surface, in particular on the skin, and which can be prepared from readily available raw materials.

Description of the invention

Surprisingly, it has been found that compounds of the general formula (I) as described in claim 1 fulfill the stated object in an excellent manner.

The present invention therefore relates to the use of compounds of general formula (I) as described in claim 1 for reducing the growth of microorganisms, in particular on a surface, as well as cosmetic and pharmaceutical formulations containing these compounds.

An advantage of the present invention is that the compounds are stable in non-polar and polar (especially alcoholic or aqueous) systems, since no hydrolysis or alcoholysis takes place under the required conditions.

Another advantage is that the effectiveness in the entire pH range of the possible cosmetic formulations is largely constant.

Another advantage is that the compounds have good skin tolerance.

Another advantage is that the compounds show good formability in common forms of application, in particular in cosmetic formulations.

All percentages (%) are percentages by weight unless otherwise specified.

The use according to the invention in the case of being used on a living species is exclusively a cosmetic and a non-therapeutic use.

wobei
R¹ = -CH₂CH₂OH, -CH₂CHOHCH₃ oder -CH(CH₃)CH₂OH,
R² = -H, -CH₂CH₂OH, -CH₃ oder -CH₂CHOHCH₃,
R³ = organischer Rest mit einer Kettenlänge von 7 oder 9 Kohlenstoffatomen
zur Reduktion des Wachstums von Mikroorganismen, insbesondere auf einer Oberfläche.The invention relates to the use of at least one compound of the general formula (I)

in which
R ¹ = -CH ₂ CH ₂ OH, -CH ₂ CHOHCH ₃ or -CH (CH ₃ ) CH ₂ OH,
R ² = -H, -CH ₂ CH ₂ OH, -CH ₃ or -CH ₂ CHOHCH ₃ ,
R ³ = organic radical having a chain length of 7 or 9 carbon atoms
to reduce the growth of microorganisms, especially on a surface.

The reduction of the growth of microorganisms can be effected either by merely inhibiting the growth and associated normal demise of the microorganisms or by killing the organisms by the compound of the general formula (I), wherein an active killing of the microorganisms is preferred. Thus, reduction of growth is preferably accompanied by a reduction in the absolute number of microorganisms in the affected area.

In the use according to the invention, R ³ may be linear or branched, saturated or unsaturated or substituted with functional groups, in particular with hydroxy groups. It is preferred in this context that R ^{3 is} an unsubstituted, linear alkyl radical.

wobei R³ insbesondere bevorzugt= -C₇H₁₅ oder -C₉H₁₉.Particularly preferably used compounds of general formula (I) are selected from the group comprising, preferably consisting of,

R ³ particularly preferably = -C ₇ H ₁₅ or -C ₉ H ₁₉ .

Very particularly preferred compounds used according to the invention are (IA) or (ID) with R ³ = -C ₇ H ₁₅ or -C ₉ H ₁₉ , where in particular (IA) with R ³ = -C ₇ H ₁₅ or -C ₉ H ₁₉ preferably used.

It is apparent that mixtures of two or more compounds of the general formula (I) can be used according to the invention.

Equally possible is the use in combination with other antimicrobial active ingredients in a concentration in which the substances according to the invention do not exhibit sufficient antimicrobial activity per se, which corresponds to use as "booster" or enhancer.

Due to the good availability of starting substances, it may be advantageous if mixtures of at least one compound of the general formula (I) and at least one compound similar to the compounds of the general formula (I) which is characterized by an R ³ having a chain length other than C7 to C9 , be used.

wobei
R¹ = -CH₂CH₂OH, -CH₂CHOHCH₃ oder -CH(CH₃)CH₂OH
R² = -H, -CH₂CH₂OH, -CH₃ oder -CH₂CHOHCH₃
R⁴ = organischer Rest mit einer Kettenlänge von kleiner 7 oder größer 9
beschrieben.Such compounds are represented by the general formula (II)

in which
R ¹ = -CH ₂ CH ₂ OH, -CH ₂ CHOHCH ₃ or -CH (CH ₃ ) CH ₂ OH
R ² = -H, -CH ₂ CH ₂ OH, -CH ₃ or -CH ₂ CHOHCH ₃
R ⁴ = organic radical with a chain length of less than 7 or greater 9
described.

In this connection, R ¹ and R ^{2 of} the general formula (I) and (II) are independent of one another, preferably R ¹ and R ² in the general formula (I) and (II) are identical.

In particular, according to the invention are preferably used mixtures of compounds of general formula I and II, which
1 to 99 (in particular 10 to 80)% by weight (IA) with R ³ = -C ₇ H ₁₅ ,
0.05 to 7 (especially 0.1 to 5) wt .-% (II) with
R ¹ = -CH ₂ CHOHCH ₃ , R ² = -H and R ⁴ = -C ₅ H ₁₁ and
0.05 to 20 (especially 0.1 to 10) wt .-% (II) with
R ¹ = -CH ₂ CHOHCH ₃ , R ² = -H and R ⁴ = -C ₁₁ H ₂₃
or
1 to 99 (in particular 10 to 80)% by weight of (IA) with R ³ = -C ₉ H ₁₉ ,
0.05 to 7 (especially 0.1 to 5) wt .-% (II) with
R ¹ = -CH ₂ CHOHCH ₃ , R ² = -H and R ⁴ = -C ₅ H ₁₁
and
0.05 to 20 (especially 0.1 to 10) wt .-% (II) with
R ¹ = -CH ₂ CHOHCH ₃ , R ² = -H and R ⁴ = -C ₁₁ H ₂₃
or
From 10 to 90 (especially 10 to 80)% by weight of (IA) with R ³ = -C ₇ H ₁₉ ,
10 to 90 (in particular 10 to 80)% by weight (IA) with R ₃ = -C ₉ H ₁₉ ,
0.2 to 7 (especially 0.5 to 5) wt .-% (II) with
R ¹ = -CH ₂ CHOHCH ₃ , R ² = -H and R ⁴ = -C ₅ H ₁₁
and
0.2 to 20 (especially 0.5 to 10) wt .-% (II) with
R ¹ = -CH ₂ CHOHOH ₃ , R ² = -H and R ⁴ = -C ₁₁ H ₂₃ , wherein here the total amount of wt .-% of the compounds (II) with
R ¹ = -CH ₂ CHOHCH ₃ , R ² = -H, R ⁴ = -C ₅ H ₁₁ and (II) with
R ¹ = -CH ₂ CHOHOH ₃ , R ² = -H, R ⁴ = -C ₁₁ H _{23 is} preferably less than 20 wt .-%,
contain, wherein here the wt .-% refer to the total amount of all compounds of the general formula I and II.

wobei R³ insbesondere bevorzugt= -C₇H₁₅ oder -C₉H₁₉ mitzuverwenden. Insbesondere bevorzugt ist in diesem Zusammenhang, dass das molare Verhältnis von verwendeten Verbindungen der allgemeinen Formel (IA) zu (IA') in einem Bereich von 90:10 bis 99:1, insbesondere von 94:6 bis 96:4 liegt.In a specific embodiment of the use according to the invention, in which compounds of the general formula (IA) are used, it is advantageous to additionally prepare at least one compound of the general formula (IA ')

wherein R ³ particularly preferably = -C ₇ H ₁₅ or -C ₉ H ₁₉ mitververwenden. In this context, particular preference is given to the molar ratio of compounds of the general formula (IA) to (IA ') used being in a range from 90:10 to 99: 1, in particular from 94: 6 to 96: 4.

Preferred R ³ for the use according to the invention of the general formula (IA) and (IA ') are those as described above for (IA); R ^{3 of} the general formula (IA) and (IA ') are independent of each other, but particularly preferred are those mixtures in which (IA) and (IA') have the same radical R ³ .

Again, it may be advantageous to use mixtures of different compounds of the general formula (IA) and (IA ') and optionally the general formula (II).

Mixtures preferably used according to the invention therefore contain:
1 to 99 (in particular 10 to 80)% by weight (IA),
0.01 to 10 (especially 0.02 to 5) wt .-% (II) with
R ¹ = -CH ₂ CHOHCH ₃ , R ² = -H and R ⁴ = -C ₅ H ₁₁ ,
0.01 to 20 (especially 0.02 to 10) wt .-% (II) with
R ¹ = -CH ₂ CHOHCH ₃ , R ² = -H and R ⁴ = -C ₁₁ H ₂₃ ,
0.02 to 20 (especially 0.04 to 10) wt .-% (IA '),
0.001 to 5 (especially 0.002 to 3) wt .-% (II) with R ¹ = -CH (CH ₃ ) CH ₂ OH, R ² = -H and R ⁴ = -C ₅ H ₁₁ and
0.001 to 5 (especially 0.002 to 3) wt .-% (II) with R ¹ = -CH (CH ₃ ) CH ₂ OH, R ² = -H and R ⁴ = -C ₁₁ H ₂₃
wherein here the total amount of wt .-% of the compounds (II) with
R ¹ = -CH ₂ CHOHCH ₃ , R ² = -H, R ⁴ = -C ₅ H ₁₁ and (II) with
R ¹ = -CH ₂ CHOHOH ₃ , R ² = -H, R ⁴ = -C ₁₁ H ₂₃ preferably less than 20 wt .-% and wherein here the wt .-% based on the total amount of all compounds of the general formula I and II and wherein R ³ for (IA) and (IA ') is preferably independently selected from -C ₇ H ₁₅ and -C ₉ H ₁₉ .

Furthermore, preference is given to using those compounds of the general formula (I) or mixtures of compounds of the general formula (I) which have a calculated octanol / water partitioning coefficient (log P) of from -1 to 4, in particular from 0 to 3.5 preferably between 0.7 and 3.0.

For example, the log P can be used with the US Environmental Protection Agency's KOWWIN v1.67 program ( www.epa.gov ) be calculated.

For mixtures of substances, the calculated log P is determined from the log P (i) of the individual components i, weighted by the proportion of component i in% by weight x (i):

By the use according to the invention of the substances, for example, the number of microorganisms in a solution, in particular in a cosmetic or pharmaceutical formulation, can be reduced. This corresponds to the basic idea of a preservative. Preferably, however, the use according to the invention is carried out on a surface.

The surface in the use according to the invention is preferably the surface of a human or animal body part, in particular the skin, the hair or the teeth.

On these surfaces are usually undesirable microorganisms such as bacteria, especially Corynebacterium xerosis, Corynebacterium jeikeium, Corynebacterium minutissimum, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus sobrinus and Streptococcus mutans. Also fungi (including yeasts), such as representatives of the genera Microsporum, Epidermiphyton, Trichphyton, as well as Candida albicans or Malassezia furfur. Thus, a use, characterized in that it is in the microorganisms Gram-positive, especially coryneform bacteria, as well as in particular also the aforementioned species, is preferred.

In a further preferred embodiment of the use according to the invention, the surface on which the use takes place is the surface of a non-living article. Examples of such surfaces are surfaces of tiles, wood, glass, ceramics, linoleum, plastic, painted surfaces, leather, fabrics, fibers. Such articles preferably come into contact several times daily directly or indirectly through humans or animals. Preferably, the surface of such objects undergoes contamination by the aforementioned contact. Examples of such items are windowpanes and benches, shower enclosures, floors such as carpets, tiles, laminates, parquet, cork floors, marble, stone and porcelain stoneware household ceramics such as WCs, wash basins, bidets, shower trays, bathtubs, door handles, faucets, household tools such as washing machines, Dryers, dishwashers, sinks of ceramic or stainless steel, furniture such as tables, chairs, shelves, shelves, windows, cookware, crockery and cutlery, laundry, in particular body-hugging underwear, watercraft, driving and airplanes such as cars, buses, Motor and sailboat tools such as surgical instruments, vacuum cleaners. Machines, pipelines, tanks and equipment for transport, processing and storage in food processing.

Thus, in this context, the use of the compounds of general formula (I) in cleaning and care products for the household, industrial and institutional industries.

The compounds of the general formula (I) are preferably used according to the invention in the form of a formulation. Further preferred uses are, in particular, those uses which make use of the formulations described below, in particular the preferred formulations described below.

wobei
R¹ = -CH₂CH₂OH, -CH₂CHOHCH₃ oder -CH(CH₃)CH₂OH,
R² = -H, -CH₂CH₂OH, -CH₃ oder -CH₂CHOHCH₃
R³ = organischer Rest mit einer Kettenlänge von 7 oder 9 Kohlenstoffatomen.It is a further subject of the invention a formulation containing at least one compound of general formula (I)

in which
R ¹ = -CH ₂ CH ₂ OH, -CH ₂ CHOHCH ₃ or -CH (CH ₃ ) CH ₂ OH,
R ² = -H, -CH ₂ CH ₂ OH, -CH ₃ or -CH ₂ CHOHCH ₃
R ³ = organic radical having a chain length of 7 or 9 carbon atoms.

In the event that the surface on which the formulation according to the invention is to be used is a living species, formulations according to the invention are preferably cosmetic or pharmaceutical formulations.

Cosmetic or pharmaceutical formulations according to the invention may find use as skin care, face care, head care, personal care, intimate care, foot care, hair care, nail care, dental care, lip care or oral care products. Examples of hair care products are shampoos, hair conditioners, hair conditioners, hair fluid, hair gel, hair tonic, hair wax, hair lacquer, hair spray, hair cream, hair mousse, hair balm, anti-dandruff shampoo. Examples of personal care products include shower bath, cream bath, cream gel, shower oil, body wash, body wash, face scrub, eye cream, night cream, cleansing mask, lotion pads, cleansing wipes, cleansing lotion, cleansing milk, cleansing gel, aftershave gel, aftershave balm , Suntan lotion, after sun products, self-tanner, foot lotion, foot spray, body lotion, body gel, body spray, body milk, body scrub, body oil, body butter.

Examples of lip care products are lip balm, lip cream, lip balm.

The cosmetic or pharmaceutical formulations of the invention may, for. B. contain at least one additional component selected from the group of
emollients,
emulsifiers,
Thickeners / viscosity regulators / stabilizers,
UV light protection filters,
antioxidants
Hydrotropes (or polyols),
Solids and fillers,
film formers,
pearlescent,
Deodorant and antiperspirant active ingredients,
insect repellents,
Self,
Preservatives,
conditioners,
perfumes,
dyes,
cosmetic agents,
Care additives,
superfatting agents,
Solvent.

Substances which can be used as exemplary representatives of the individual groups are known to the person skilled in the art and can be used, for example, in the German application DE 10 2008 001 788.4 be removed. This patent application is hereby incorporated by reference and thus forms part of the disclosure.

In the case of the use of the compounds of general formula (I) in the form of a formulation on non-living surfaces are in particular cleaning and care products for household, industrial and institutional applications such as disinfectants, disinfectant cleaners, foam cleaners, floor cleaners, carpet cleaners, upholstery cleaners , Floor care products, marble cleaners, parquet cleaners, stone and ceramic floor cleaners, mop cleaners, stainless steel cleaners, glass cleaners, dishwashing detergents, plastic cleaners, sanitary cleaners, wood cleaners, leather cleaners, detergents, laundry detergents disinfectant detergents, heavy-duty detergents, mild detergents, wool detergents, fabric softeners, impregnating agents.

It is apparent that mixtures of compounds of the general formula (I) can be present in formulations according to the invention. It is advantageous if such a formulation is characterized by containing mixtures of compounds in which R ^{3 has} 7 and 9 carbon atoms; In particular, a preferred weight ratio of compounds of the general formula (I) with an R ³ having 7 carbon atoms to compounds of the general formula (I) with an R ³ having 9 carbon atoms is in a range from 5:95 to 95: 5, more preferably from 35:65 to 65:35.

However, it has been found that the presence of a high proportion of the compounds of the general formula (I) similar compounds characterized by an R ³ with different chain length than C7 to C9 has a negative impact on the reduction of the number of nuclei.

wobei
R¹ = -CH₂CH₂OH, -CH₂CHOHCH₃ oder -CH(CH₃)CH₂OH,
R² = -H, -CH₂CH₂OH, -CH₃ oder -CH₂CHOHCH₃,
R⁴ = organischer Rest mit einer Kettenlänge von kleiner 7 oder größer 9
bezogen auf die Gesamtmenge der Verbindungen der allgemeinen Formel (I) und (II)
enthalten sind. Therefore, preferred formulations according to the invention are characterized in that in the formulation less than 80% by weight, preferably less than 40% by weight, in particular less than 20% by weight, of compounds of the general formula (II)

in which
R ¹ = -CH ₂ CH ₂ OH, -CH ₂ CHOHCH ₃ or -CH (CH ₃ ) CH ₂ OH,
R ² = -H, -CH ₂ CH ₂ OH, -CH ₃ or -CH ₂ CHOHCH ₃ ,
R ⁴ = organic radical with a chain length of less than 7 or greater 9
based on the total amount of the compounds of the general formula (I) and (II)
are included.

In this connection, R ¹ and R ^{2 of} the general formula (I) and (II) are independent of one another, preferably R ¹ and R ² in the general formula (I) and (II) are identical.

It has been found that formulations according to the invention comprising mixtures of compounds of the general formula (I) and (II) which have a calculated octanol-water partitioning coefficient (log P) of from -1 to 4, in particular from 0 to 3.5, are particularly preferred between 0.7 and 3.0 are particularly preferred. In this context, the calculated log P as described above from the log P (i) of the individual components i, weighted by the proportion of component i in wt .-% x (i) determined using the program KOWWIN v1.67.

wobei
R³ = -C₇H₁₅ oder -C₉H₁₉.Formulations according to the invention preferably contain compounds of the general formula (I) selected from the group comprising, preferably consisting of,

in which
R ³ = -C ₇ H ₁₅ or -C ₉ H ₁₉ .

Further preferred formulations according to the invention preferably contain those compounds or mixtures of the general formula (I) which, as described above, are preferably used according to the invention for reducing the growth of microorganisms.

Formulations according to the invention are characterized in particular in that they contain from 0.001% by weight to 10% by weight, preferably from 0.01% by weight to 7% by weight, particularly preferably from 0.05% by weight to 3% by weight. % of at least one compound of general formula (I) based on the total formulation.

The compounds of the invention can be used in a variety of formulations for household, industrial, pharmaceutical and cosmetic applications. They are particularly suitable as effective components in deodorants, which may be in the form of aerosol sprays, pump sprays, roll-on formulations, deodorant sticks, W / O or O / W emulsions (eg creams or lotions) or wipes , Can be used in these formulations known from the prior art agents / drug combinations such. Triclosan, ethylhexylglycerol, aluminum chlorohydrate, aluminum zirconium tetrachlorohydrex GLY, aluminum zirconium pentachlorohydrate, farnesol, polyglycerine caprylate or caprylate, triethyl citrate, penta (carboxymethyl) diethylenetriamine (pentetic acid), pentylene glycol, propylene glycol, ethanol, zinc ricinoleate, cyclodextrins, alum, silver and its salts or zinc oxide.

However, the application is not limited to the use in deodorants, but may be advantageous wherever a control of microorganisms or their growth is desired, such as As in intimate hygiene products, anti-acne or anti-dandruff products, which may be in the form of the usual leave-on or rinse-off formulations, such as. As creams, lotions, shampoos, washing solutions, hair rinses, wipes and similar formulations.

The use of the formulations according to the invention in footcare agents is also advantageous; foot care products are understood not only to be applied directly to the skin compositions, but the term includes, for example, also deodorant shoe inserts.

For antiacne products, the substances according to the invention may optionally also be used in combination with known antiacne agents, such as. As dibenzoyl peroxide, salicylic acid, phytosphingosine, tretinoin, isotretinoin or plant extracts. Similarly, in the case of anti-dandruff products, combinations with known anti-dandruff active ingredients, such as. As climbazole, zinc pyrethione, selenium compounds (for example selenium sulfide), Piroctone olamine (Octopirox) or plant extracts.

Also in the field of oral hygiene products, the substances according to the invention can be used, whereby in particular the use in mouthwashes or toothpastes is recommended.

They may also be used for this purpose in combination with other active ingredients which have efficacy gaps in areas in which the substances of the invention are active. Thus, the use of preservatives can be reduced or possibly even completely dispensed with classical preservatives.

• a) Bereitstellung einer erfindungsgemäßen Formulierung, insbesondere einer kosmetischen oder pharmazeutischen Formulierung
• b) Applikation der Formulierung auf die zu behandelnde Oberfläche, insbesondere Haut, Haare oder Zähne in einer wirksamen Menge
• c) Belassen der Formulierung auf der zu behandelnden Oberfläche für eine Zeit, die ausreichend ist, um die Reduktion des Wachstums der Mikroorganismen zu gewährleisten und
• d) ggf. Auswaschen oder Abspülen der Formulierung.

Another object of the invention is a method for reducing the growth of microorganisms, comprising the steps

• a) providing a formulation according to the invention, in particular a cosmetic or pharmaceutical formulation
• b) application of the formulation to the surface to be treated, in particular skin, hair or teeth in an effective amount
• c) leaving the formulation on the surface to be treated for a time sufficient to ensure the reduction of the growth of the microorganisms, and
• d) optionally rinsing or rinsing the formulation.

In the examples given below, the present invention is described by way of example, without the invention, the scope of application of which is apparent from the entire description and the claims, to be limited to the embodiments mentioned in the examples.

The following figures are part of the examples:

1 : Antimicrobial effect depending on the calculated log P

2 : Antimicrobial effect of isopropanolamide mixtures of different chain lengths depending on the calculated log P

Abbreviations:

• C6-MIPA:

  Capronsäureisopropanolamid

  C8-MIPA:

  Caprylsäureisopropanolamid

  C10 MIPA:

  Caprinsäureisopropanolamid

  C12 MIPA:

  lauric

  C8-MEA:

  Caprylsäuremonoethanolamid

  C8-DEA:

  Caprylsäurediethanolamid

  C8-NMEA:

  Caprylic-N-Methylethanolamid

Examples:

The log P values were calculated using the program KOWWIN v1.67, © 2000 U. S. Environmental Protection Agency.

For mixtures of substances of the formulas (I) and (II), the calculated log P is determined from the log P (i) of the individual components i, weighted with the proportion of component i in% by weight x (i):

synthesis Examples

Example 1: Preparation of a mixture of caprylic acid-N-methylethanolamide and capric acid-N-methylethanolamide

209 g of a mixture of methyl caprylate and methyl caprate (54:42, containing 4% methyl caproate), 225 g N-methylethanolamine and 13 g of a 30% sodium methylate solution (in methanol) were stirred in a four-necked flask equipped with stirrer, gas inlet tube, thermometer and distillation bridge and nitrogen inlet heated to 110 ° C for 8 h. The resulting methanol was distilled off continuously.

After the end of the reaction, the residual amine content was determined to be 1.6% by titration with HCl.

Example 2: Preparation of a mixture of caprylic acid ethanolamide and capric acid ethanolamide

543 g of a mixture of methylcaprylate and methylcaprinate (54:42, containing 4% methyl caproate), 183 g of ethanolamine and 22 g of a 30% sodium methylate solution (in methanol) were reacted analogously to Example 1. After a reaction time of 12 h, the product had a residual amine content of 1.7%.

Example 3: Preparation of a mixture of caprylic acid isopropanolamide and capric isopropanolamide

1043 g of a mixture of methylcaprylate and methylcaprinate (54:42, containing 4% methyl caproate), 457 g of 1-amino-2-propanol and 33 g of a 30% sodium methylate solution (in methanol) were reacted analogously to Example 1. After a reaction time of 8 h, the product had a residual amine content of 2.5%.

Example 4: Preparation of a mixture of caprylic acid isopropanolamide and capric isopropanolamide

308 g of a mixture of caprylic acid and capric acid (60:40) were added dropwise over 30 minutes to 150 g of 1-amino-2-propanol. The mixture was heated with stirring and nitrogen inlet to 170 ° C, the resulting water was distilled through a distillation bridge with 10 cm Vigreux Kollone. After 2 h, a vacuum of 400 mbar was applied. After another hour, the Vigreux column was removed and a vacuum of 100 mbar was applied for 1 h.

Example 5 Antimicrobial action of individual substances

0.5 ml of a stock solution of 2 wt .-% of the test substance, 1.5 wt .-% PEG-40 Hydrogenated Castor Oil (TAGAT ^® CH 40) and 20 wt .-% ethanol in water were mixed with 0.5 ml of a Germ suspension of the test microorganism (Corynebacterium xerosis (C. x.), Approx. 105 CFU / ml) and incubated at 30 ° C. After 180 minutes, the bacterial count was determined by means of a spirometer.

The reduction of the germ count after 180 min of R180 was according to
R180 = germ count (0 min) / germ count (180 min)
calculated. log P KOWWIN R180 (C.x.) C6 MIPA 0.71 1 C8 MIPA 1.69 1650 C10 MIPA 2.68 1900 C12 MIPA 3.66 4 C8 NMEA 1.49 633 C8 MEA 1.28 1350 C8 DEA 0.92 1350

The antimicrobial effect (as R180) as a function of the calculated log P is in 1 shown.

Example 6: Antimicrobial action of mixtures

Analogously to Example 5, the antimicrobial effect of Isopropanolamidgemischen was determined with different chain distributions of the acyl radical. G1 G2 G3 G4 G5 G6 C8 50 40 30 20 10 0 C10 50 40 30 20 10 0 C12 0 12 24 37 49 61 C14 0 4 8th 11 15 19 C16 0 2 3 5 6 8th C18 0 3 5 8th 10 13 log P KOWWIN 2.19 2.63 3.08 3.53 3.98 4.42 R180 (C.x.) 1350 1350 450 28 2 1

The antimicrobial effect (as R180) as a function of the calculated log P of the mixtures is in 2 shown.

Example 7: Antimicrobial effect on various germs

Analogously to Example 5, the antimicrobial effect of C8-MIPA on various test microbes was determined. test germ Staphylococcus epidermidis Candida albicans Malassezia furfur Streptococcus mutans R180 500 10 38 2500

formulation Examples

Example 8: Deodorizing

The deodulations described below were prepared using the isopropanolamide mixture from Example 3. Deoformulations (pump sprays) 1 2 3 4 Phase A 20 ° C 50 ° C 20 ° C 50 ° C Synthesis Example 3 0.5 0.5 0.5 0.5 TEGO ^® SML 20 3 3 3 3 Fragrance 0.5 0.5 0.5 0.5 ethanol ad 100% - 30 - ABIL ^® B8832 - 0.5 - 0.5 Tegosoft ^® M 1 - - - Phase B Water ad 100% ad 100% ad 100% Tegosoft ^® GC 1 1 allantoin 0.2 0.2 panthenol 0.1 0.1 Phase C ACH Solution 501 - - 20 30 Kathon CG 0.03 0.03 0.03 0.03

Phase A was weighed in the order listed and mixed at the temperature listed in the table.

Phase B and Phase C were weighed separately at room temperature and added successively to Phase A with stirring. Deo-formulations (roll-on) 5 6 Phase A Synthesis Example 3 0.5 0.5 TEGO ^® SML 20 3 3 Fragrance 0.5 0.5 ethanol 20 20 ABIL ^® B8832 0.5 0.5 Tegosoft ^® GC 1 1 Phase B Water ad 100% ad 100% Hydroxyethyl cellulose 0.75 0.75 Water (for swelling of hydrocolloid) 36.75 36.75 allantoin 0.1 0.1 panthenol 0.2 0.2 Phase C ACH Solution 501 - 20 Kathon CG 0.03 0.03

Phase B was weighed in the order listed, stirred until uniform dispersion of the hydroxycellulose and allowed to stand until complete swelling of the polymer. Phase A was weighed in the order listed and mixed at 50 ° C. Phase B and C were added successively to Phase A with stirring. Example 9: Anti-acne facial cleansing lotion INCI name Wt .-% PEG-40 Hydrogenated Castor Oil 01.05% Perfume 0.1% PEG-6 Caprylic / Capric Glycerides 01.05% ethanol 5.0% Caprylic / Capramidopropyl Betaine 05.02% allantoin 0.3% water 86.2% Synthesis Example 3 0.2% preservative qs

Preparation: PEG-40 Hydrogenated Castor Oil was charged and heated to about 40 ° C until clear. Subsequently, the remaining ingredients of the recipe were added step by step with stirring. The product from Synthesis Example 3 was melted before addition. Example 10: Moisturizing Anti-Acne Facial Cleansing Gel INCI name Wt .-% water 55.2% glycerin 10.0% Carbomer 01.06% Synthesis Example 3 0.3% Sodium Laureth Sulfate, 28% 04.21% TEGO Betain F50 05.03% Perfume 0.2% Sodium hydroxides, 10% 6.0% preservative qs

Preparation: Water and glycerin were mixed. Then the carbomer was added slowly with vigorous stirring and continued stirring until completely swollen. Subsequently, the remaining ingredients of the recipe were added step by step. The product from Synthesis Example 3 was melted before addition. Example 11: Anti-Acne Face Cream INCI name Wt .-% Phase A Polyglyceryl-3 methylglucose 3.0% Distearate Glyceryl stearate 2.0% Stearyl Alcohol 1.0% Cyclopentasiloxane 6.0% Ethylhexyl stearate 5.0% Diethylhexyl carbonates 3.0% phytosphingosine 0.1% Synthesis Example 3 0.2% Phase B glycerin 3.0% water 76.5% Phase C Perfume 0.2% preservative qs

Preparation: Phase A and B were heated separately to 80 ° C. Subsequently, phase B was added to A and homogenized. Then the emulsion was cooled with stirring to about 30 ° C. The perfume was added during the cooling process below 40 ° C. Example 12: Anti-Acne Facial Lotion INCI name Wt .-% Phase A Glyceryl Stearate Citrate 01.05% Cetearyl Alcohol 1.0% Caprylic / Capric Triglycerides 08.05% Myristyl myristate 4.0% Tocopheryl acetate 1.0% Almond (Prunus Dulcis) Oil 1.0% Synthesis Example 3 0.1% Phase B glycerin 5.0% water 76.9% Phase C Carbomer 0.2% Ethylhexyl stearate 0.8% Phase D Sodium hydroxides, 10% qs Phase Z preservative qs Perfume qs

Preparation: Phase A and B were heated separately to 80 ° C. Subsequently, phase B was added to A and homogenized. Then the emulsion was cooled to 60 ° C with stirring and Phase C was added. It was briefly homogenized again. The emulsion was further cooled with stirring to about 30 ° C. Phase D and then Phase Z were added during the cooling process below 40 ° C. Example 13: Antidandruff Shampoo INCI name Wt .-% Sodium Laureth Sulfate, 28% 32.0% Perfume 0.3% water 57.5% Synthesis Example 3 0.2% Cocoamidopropyl Betaine, 37.5% 8.0% PEG-18 Glyceryl Oleate / Cocoate 2.0% NaCl qs preservative qs

Preparation: The ingredients of the antidandruff shampoo were mixed successively without heating with stirring.

The product of Synthesis Example 3 was melted before processing. Example 14: Nourishing anti-dandruff shampoo INCI name Wt .-% Phase A Glycol distearate 3.0% Sodium Laureth Sulfate, 28% 40.0% Phase B Perfume 0.3% Zinc Pyrithione, 48% 2.0% Quaternium-80 1.0% Phase C water 36.6% Synthesis Example 3 0.3% Acrylates / C10-30 alkyl acrylates 0.2% Crosspolymer Polyquaternium-10 0.3% NaOH, 10% 0.3% Phase D Undecylenamidopropyl betaines 05.12% Isostearamide MIPA 03.05% Phase Z preservative qs

Preparation: Phase A was heated to about 65 ° C until the glycol distearate was melted and then cooled to 45 ° C. Then, the ingredients of Phase B were added to Phase A, step by step, in the order given.

To prepare Phase C, the carbomer was dispersed in water and stirred until completely swollen. Subsequently, Polyquaternium-10 was added and stirred until it was also completely swollen. Then neutralization with NaOH.

Subsequently, Phase C was added to the remainder of the formulation. Lastly, the ingredients of Phase D and Phase Z were added sequentially. The product of Synthesis Example 3 was melted before processing. Example 15: Clear anti-dandruff shampoo INCI name Wt .-% Sodium Laureth Sulfate, 28% 32.0% Piroctone Olamine 0.5% Perfume 0.3% Dimethicone Propyl PG-Betaine 0.5% water 56.3% Synthesis Example 3 0.2% Cocamidopropyl Betaine 37.5% 8.0% Cocamidopropyl Betaine, Glyceryl 02.02% Laurate NaCl qs preservative qs

Preparation: The ingredients of the formulation were mixed without heating step by step in the order listed. The product from Synthesis Example 3 was previously melted in a water bath. Example 16: Nourishing antidandruff shampoo for severely damaged hair INCI name Wt .-% Phase A Sodium Laureth Sulfate, 28% 32.0% Palmitamidopropyltrimonium Chloride 01.05% PEG-100 Hydrogenated Glyceryl 02.02% palmate; PEG-7 glyceryl cocoate Quaternium-80 2.0% Perfume 0.3% Phase B water 54.9% Synthesis Example 3 0.3% Polyquaternium-10 0.3% Phase C Cocamidopropyl betaine, 47% 06.05% Phase Z NaCl qs preservative qs

Preparation: The ingredients of Phase A were mixed step by step. The product of Synthesis Example 3 was melted prior to processing and dispersed in the water phase. Subsequently, the polyquaternium-10 was added and the solution was stirred until completely swollen. Subsequently, Phase B was added to Phase A. Finally, phases C and Z were added sequentially. Example 17: Clear hair tonic with anti-dandruff action INCI name Wt .-% PEG-40 Hydrogenated Castor Oil 1.0% Perfume 0.2% Quaternium-80 0.4% Dimethicone Propyl PG-Betaine 0.6% Cetrimonium chlorides 0.3% water 82.25% Synthesis Example 3 0.05% Creatine 0.2% ethanol 15.0% preservative qs

Preparation: PEG-40 Hydrogenated Castor Oil was heated to about 40 ° C until it was clear. Then the remaining ingredients of the formulation were added step by step without heating. The product of Synthesis Example 3 was melted before processing. Example 18: Deodorant foot spray with propane / butane INCI name Wt .-% Cyclomethicone 07.04% PEG-8 07.04% Alcohol 89.1% Polyglyceryl-3-caprylates 01.03% Synthesis Example 3 0.2% Perfume qs

Aerosol Filling:

• 30% solution
• 70% blowing agent

Preparation: The ingredients of the formulation were mixed without heating step by step in the order listed with stirring. The product of Synthesis Example 3 was melted before processing. Example 19: Further Deoformulations: Antiperspirant Spray INCI name Wt .-% Phase A PEG-40 Hydrogenated Castor Oil 1.0% Perfume 0.3% Alcohol 20.0% Phase B Betaine 2.0% water 56.3% Synthesis Example 3 0.3% allantoin 0.1% Aluminum zirconium 20.0% Tetrachlorohydrate, 35% preservative qs

Preparation: Phase A was heated to 50 ° C. The product of Synthesis Example 3 was melted prior to processing and dispersed in the water phase.

Subsequently, phase B was added without heating. Example 20: Further Deoformulations: Roll-on INCI name Wt .-% Phase A Steareth-2 02.02% Stearath-20 1.0% Cetearyl ethylhexanoate 2.0% PPG-11 stearyl ether 2.0% Dimethicone 0.5% Zinc ricinoleate 1.0% Phase B glycerin 3.0% water 88.1% Synthesis Example 3 0.2% Phase Z preservative qs Perfume qs

Preparation: Phase A and B were heated to 80 ° C. Then Phase B was added to A and homogenized. The mixture was then cooled to 30.degree. C. while stirring and phase Z was added. Example 21: Clear Emollient Stick INCI name Wt .-% PPG-3 myristyl ether 69.4% Propylene glycol 05.13% water 4.0% Synthesis Example 3 0.1% Sodium stearate 8.0% Cocamide DEA 5.0% preservative qs

Preparation: The ingredients were mixed step by step at 80 ° C in the order given. The mixture was then cooled to 75 ° C. while stirring and the product was filled into the stick sleeves. Example 22: Further Deo-formulations: PEG-free antiperspirant lotion INCI name Wt .-% Phase A Methyl glucose sesquistearate 1.75% Polyglyceryl-4 Laurate 0.25% Diethylhexyl carbonates 03.05% PPG-14 butyl ether 03.05% Polyglyceryl-3-caprylates 0.5% Phase B water 74.3% Synthesis Example 3 0.2% Hydroxyethyl cellulose 1.0% Phase C Aluminum Chlorohydrate 15.0% Phase Z preservative qs Perfume qs

Preparation: Phase A and B were heated to 70-75 ° C. Then Phase B was added to A and homogenized. With stirring, it was then cooled to 30 ° C. During the cooling process, Phase C was added below 40 ° C. Example 23: O / W lotion for Wipes (suitable for acne skin) INCI name Wt .-% Phase A Glyceryl stearates; Ceteth-20 3.0% Stearyl Alcohol 1.0% Ethylhexyl stearate 6.0% C12-15 alkyl benzoates 5.0% Phase B water 81.7% glycerin 3.0% Phytosphingosine HCl 0.2% Synthesis Example 3 0.1% Phase Z preservative qs Perfume qs

Preparation: Phase A and B were heated to 80 ° C. Then Phase B was added to A and homogenized. With stirring, the emulsion was then cooled to 30 ° C. Example 24: Watering Solution for Wipes INCI name Wt .-% Polysorbate 80 3.0% Perfume 0.3% Bis-PEG / PPG-20/20 Dimethicone 0.5% water 91.4% Creatine 0.5% Synthesis Example 3 0.2% panthenol 0.1% propylene glycol 4.0% Citric acid, 10% qs preservative qs

Preparation: The ingredients of the formulation were mixed step by step in the order listed. The product of Synthesis Example 3 was melted before processing. Finally, the pH was adjusted to 6.5 with citric acid. Example 25: Soaking solution for facial cleansing wipes INCI name Wt .-% PEG-40 Hydrogenated Castor Oil 2.0% Perfume 0.2% Bis-PEG / PPG-20/20 Dimethicone 0.5% Disodium Laureth Sulfosuccinate 02.05% water 93.4% panthenol 0.1% Sodium cocoamphoacetate 1.0% Synthesis Example 3 0.3% preservative qs

Preparation: PEG-40 Hydrogenated Castor Oil was heated to 40 ° C until clear. Then the remaining ingredients of the formulation were added step by step with stirring in the order listed.

The product of Synthesis Example 3 was melted before processing. Example 26: Surface Disinfectant ingredient Wt .-% N-alkyl aminopropyl glycine (REWOCID ^® WK 30) 66.6% water 18.0% Monoethanolamine 03.13% Synthesis Example 3 2.0%

The ingredients are mixed with stirring at about 60 ° C. Example 27: Disinfecting surface cleaner ingredient Wt .-% Amphoteric alkylamino carboxylates (and) alkylbetaines (TEGOTAIN ^® AFB) 10.0% water 85.0% Propylene glycol 3.0% Synthesis Example 3 2.0%

The product of Synthesis Example 3 is heated with gentle heating in propylene glycol. The ingredients are mixed with stirring at about 60 ° C.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• US 5407668 [0008]
• WO 9635767 [0009]
• DE 2432882 [0009]
• JP 2000191511 [0009]
• US 3385755 [0010]
• GB 2354771 [0010]
• JP 2001214368 [0010]
• DE 102008001788 [0050]

Cited non-patent literature

• www.epa.gov [0037]

Claims (17)

Use of at least one compound of the general formula (I)

wherein R ¹ = CH ₂ CH ₂ OH, -CH ₂ CHOHCH ₃ or -CH (CH ₃ ) CH ₂ OH, R ² = -H, -CH ₂ CH ₂ OH, -CH ₃ or -CH ₂ CHOHCH ₃ , R ³ = organic residue with a chain length of 7 or 9 carbon atoms to reduce the growth of microorganisms. Use according to claim 1, characterized in that the compound of general formula (I) is selected from the group comprising

Use according to claim 1 or 2, characterized in that the compounds of general formula (I), (IA) to (IE) with R ³ = -C ₇ H ₁₅ or -C ₉ H ₁₉ are used. Use according to Claim 2 or 3, characterized in that compounds of the general formula (IA) and additionally at least one compound of the general formula (IA ')

in particular in a molar ratio of (IA) to (IA ') in a range from 90:10 to 99: 1. Use according to at least one of the preceding claims, characterized in that the compound of general formula (I) or the mixtures of compounds of general formula (I) used have a calculated octanol-water partitioning coefficient (log P) of -1 to 4 , Use according to at least one of the preceding claims, characterized in that the microorganisms are Corynebacterium xerosis, Corynebacterium jeikeium, Corynebacterium minutissimum, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus sobrinus, Streptococcus mutans, Candida albicans, Malassezia furfur the genera Microsporum, Epidermiphyton, Trichphyton or Gram-positive, especially coryneform, bacteria. Formulation containing at least one compound of general formula (I)

in which R ¹ = CH ₂ CH ₂ OH, -CH ₂ CHOHCH ₃ or -CH (CH ₃ ) CH ₂ OH, R ² = -H, -CH ₂ CH ₂ OH, -CH ₃ or -CH ₂ CHOHCH ₃ , R ³ organic residue with a chain length of 7 or 9 carbon atoms. A formulation according to claim 7, characterized in that in the cosmetic formulation less than 80 wt .-% of compounds of general formula (II)

wherein R ¹ = CH ₂ CH ₂ OH, -CH ₂ CHOHCH ₃ or -CH (CH ₃ ) CH ₂ OH, R ² = -H, -CH ₂ CH ₂ OH, -CH ₃ or -CH ₂ CHOHCH ₃ R ⁴ = organic radical having a chain length of less than 7 or greater than 9 based on the total amount of the compounds of the general formula (I) and (II) are contained. A formulation according to claim 7 or 8, characterized in that the compound of general formula (I) is selected from the group comprising

where R ³ = -C ₇ H ₁₅ or -C ₉ H ₁₉ . A formulation according to any one of claims 7 to 9, characterized in that it contains 0.001 to 10 wt .-% of at least one compound of general formula (I) based on the total formulation. Cosmetic or pharmaceutical formulation according to at least one of claims 7 to 10, characterized in that it is an antiperspirant or deodorant formulation, preferably in the form of an aerosol spray, a pump spray, a roll-on formulation, a deodorant stick, a W / O or O / W emulsion or a wipe. Cosmetic or pharmaceutical formulation according to at least one of claims 7 to 10, characterized in that it is an oral hygiene product, in particular mouthwash or toothpaste. Cosmetic or pharmaceutical formulation according to at least one of claims 7 to 10, characterized in that it is an intimate hygiene article. Cosmetic or pharmaceutical formulation according to at least one of claims 7 to 10, characterized in that it is a foot care product. A pharmaceutical formulation according to any one of claims 7 to 10 for the treatment of acne. Cosmetic or pharmaceutical formulation according to any one of claims 7 to 10 for the treatment of dandruff. Formulation according to at least one of claims 7 to 10, characterized in that it is a cleaning and care product for household, industrial or institutional applications.

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