EP2435036A2 - Ammoniumcarboxylates - Google Patents

Ammoniumcarboxylates

Info

Publication number
EP2435036A2
EP2435036A2 EP10721308A EP10721308A EP2435036A2 EP 2435036 A2 EP2435036 A2 EP 2435036A2 EP 10721308 A EP10721308 A EP 10721308A EP 10721308 A EP10721308 A EP 10721308A EP 2435036 A2 EP2435036 A2 EP 2435036A2
Authority
EP
European Patent Office
Prior art keywords
ethyl
dimethyl
methyl
methoxyethylammonium
hydroxyethylammonium
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP10721308A
Other languages
German (de)
French (fr)
Inventor
William-Robert Pitner
Jens Eichhorn
Thomas Rudolph
Uschi Schmid-Grossmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Patent GmbH
Original Assignee
Merck Patent GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck Patent GmbH filed Critical Merck Patent GmbH
Priority to EP10721308A priority Critical patent/EP2435036A2/en
Publication of EP2435036A2 publication Critical patent/EP2435036A2/en
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
    • A01N33/02—Amines; Quaternary ammonium compounds
    • A01N33/12—Quaternary ammonium compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
    • A01N33/16—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds containing nitrogen-to-oxygen bonds
    • A01N33/18—Nitro compounds
    • A01N33/20—Nitro compounds containing oxygen or sulfur attached to the carbon skeleton containing the nitro group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/41—Amines
    • A61K8/416—Quaternary ammonium compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C215/40—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton with quaternised nitrogen atoms bound to carbon atoms of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
    • C07C217/08—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to an acyclic carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
    • C07C69/12—Acetic acid esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
    • C07C69/22—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety
    • C07C69/24—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety esterified with monohydroxylic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q15/00—Anti-perspirants or body deodorants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/004—Preparations used to protect coloured hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/006—Antidandruff preparations

Definitions

  • the present invention relates to special ammonium carboxylates, their synthesis and their application, particularly as biocides.
  • Contamination of living organisms like microbial, fungicidal or algicidal contamination is an essential concern in our daily life, whether it concerns cosmetic products, surface areas e.g. in bathrooms, hospitals or clean rooms, surgical instruments or wall paints.
  • the usage of biocides is a common method for preventing contamination of living organisms.
  • a biocide is a chemical substance capable of killing living organisms, usually in a selective way.
  • Biocides are commonly used in medicine, agriculture, forestry and in industry where they prevent e.g. the fouling of water and oil pipelines. Some substances used as biocides are also employed as anti-fouling agents or disinfectants under other circumstances. Biocides can be added to other materials or substrates, typically liquids, to protect them against biological infestation and growth.
  • the Biocidal Products Directive 98/8/EC (BPD), the classification of biocides, is broken down into 23 product types (i.e. application categories), with several comprising multiple subgroups.
  • the four main groups are "disinfectants and general biocidal products”, “preservatives”, “pest control” and “other biocidal products” with the subgroups “preservatives for food or feedstocks”, “antifouling products”, “embalming and taxidermist fluids” and "control of other vertebrates”.
  • biocides especially as disinfectants or preservatives.
  • a special class of ammonium carboxylates are especially useful as biocides.
  • R is alkoxymethyl or alkoxyethyl in which the alkoxy group is linear or branched and has 1 to 4 C atoms, hydroxy methyl, hydroxyethyl, hydroxypropyl or hydroxybutyl
  • R 1 to R 3 are independantly of each other linear or branched alkyl with 1 to 4 C atoms
  • R 4 is linear or branched alkyl with 5 to 11 C atoms, wherein the compound N,N,N-trimethyl-2-hydroxyethylammonium hexanoate is excluded.
  • N,N,N-Trimethyl-2-hydroxyethylammonium hexanoate is described as solvent for refined cork dissolution, particularly with respect to the separation of large quantities of suberin, in H. Garcia et al, Green Chem., 2010, 12, 367-369.
  • ionic liquids are ionic species which consist of an organic cation and a generally inorganic or organic anion. They preferably do not comprise neutral molecules and usually have melting points below 373 K. In the context of this patent application the term "ionic liquid” is used as a synonym to chemical compound or compound.
  • the linear or branched alkyl group with 1 to 4 C-atoms is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl or tert.-butyl.
  • the linear or branched alkyl group with 5 to 11 C-atoms is, for example, n- pentyl, methylbutyl, n-hexyl, ethylbutyl, methylpentyl, n-heptyl, n-octyl, ethylhexyl, n-nonyl, n-decyl or n-undecyl.
  • the linear or branched alkoxy group with 1 to 4 C-atoms is, for example, methoxy, ethoxy, isopropoxy, propoxy, butoxy, sec-butoxy or tert-butoxy.
  • the subsitutent R 4 in formula I is preferably linear alkyl with 5 to 11 C- atoms, particularly preferably n-pentyl, n-hexyl, n-heptyl or n-undecyl, very particularly preferably n-heptyl.
  • the substituents R 1 to R 3 in the compounds of the formula I may be identical or different. Preferably two substituents are identical and one substituent is different.
  • the substituents R 1 to R 3 are independantly of each other preferably methyl or ethyl. Particularly preferably, two substituents of R 1 to R 3 are methyl and the other substituent is ethyl or two substituents of R 1 to R 3 are ethyl and the other substituent is methyl. Very particularly preferably, two substituents of R 1 to R 3 are methyl and the other substituent is ethyl.
  • the substituent R is preferably methoxyethyl, ethoxyethyl or hydroxyethyl.
  • Preferred compounds of formula I are N-ethyl-N,N-dimethyl-2-methoxyethylammonium hexanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium hexanoate, N-ethyl-N,N-dimethyl-2-methoxyethylammonium octanoate, - A -
  • N-ethyl-N,N-dimethyl-2-methoxyethylammonium decanoate N-ethyl-N,N-dimethyl-2-methoxyethylammonium dodecanoate, N-ethyl-N,N-dimethyl-2-hydroxyethylammonium hexanoate, N-ethyl-N,N-dimethyl-3-hydroxypropylammonium hexanoate, N-ethyl-N,N-dimethyl-4-hydroxybutylammonium hexanoate,
  • N-ethyl-N,N-dimethyl-2-hydroxyethylammonium octanoate N-ethyl-N,N-dimethyl-2-hydroxyethylammoniunn decanoate N-ethyl-N,N-dimethyl-2-hydroxyethylammonium dodecanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium hexanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium octanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium decanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium dodecanoate, N,N-diethyl-N -methyl-2-methoxyethylammonium hexanoate, N,
  • N-ethyl-N,N-dimethyl-2-methoxyethylammonium octanoate N-ethyl-N,N-dimethyl-2-hydroxyethylammonium octanoate.
  • the invention likewise relates to a process for the production of compounds of formula I, as described above, in which ammonium halides of formula Il
  • ammonium halides of formula Il may be synthesized by reaction of corresponding amines NRR 1 R 2 with haloalkanes HaIR 3 in solvents at temperatures between 10 and 100 0 C.
  • Typical solvents are acetonitrile, isopropanol, toluene, heptane or cyclohexane.
  • the reaction may also be carried out in the absence of a solvent or using an excess of one of the two reagents as the solvent.
  • a typical ion exchange resin which can be used in the inventive process is Merck Product Nr. 104767 Ion Exchanger III (strongly basic anion exchanger, OH-Form) for Analysis. All other ion exchange resins which have the same or similar properties as this strongly basic anion exchanger can be used.
  • the ion exchange typically takes place using water as the solvent for the ammonium halide.
  • Useful solvents other than water are methanol, ethanol, propanol, butanol, isopropanol and isobutanol.
  • the corresponding solution of the ammonium hydroxide is reacted with R 4 COOH to form the compound of formula I.
  • the substituents R, R 1 to R 4 have the meaning as described above.
  • the present invention furthermore relates to the use of the said ionic liquids of formula I as solvent or solvent additive, as phase-transfer catalyst, as extractant, as heat-transfer medium, as surface-active substance, as plasticiser, as flame retardant, as supporting electrolyte or additive in electrochemical cells.
  • ionic liquids as solvents, these are suitable in any type of reaction known to the person skilled in the art, for example for transition-metal- or enzyme-catalysed reactions, such as, for example, hydroformylation reactions, oligomerisation reactions, esterifications or isomerisations, where the said list is not exhaustive.
  • the ionic liquid can be employed to separate off reaction products, but also to separate off impurities, depending on the solubility of the respective component in the ionic liquid.
  • the ionic liquids may also serve as separation media in the separation of a plurality of components, for example in the distillative separation of a plurality of components of a mixture.
  • plasticiser in polymer materials, as flame retardant for a number of materials or applications, and as a supporting electrolyte or additive in various electrochemical cells and applications, for example in galvanic cells, in capacitors or in fuel cells.
  • ionic liquids are solvents for carbohydrate containing solids in particular biopolymers and derivatives or degredation products thereof.
  • these new compounds can be applied as lubricants, working fluids for maschines, such as compressors, pumps or hydraulic devices.
  • the ionic liquids according to this invention may be also used in electro-chemical cells in particular for electro-optical cells or as functional materials in sensors.
  • ionic liquids of formula I are the use as biocides as defined above.
  • the ionic liquids according to the present invention can be used for the inhibition of the growth and/or progeny of microorganisms preferably in order to preserve compositions.
  • it may be of particular interest to inhibit the growth of undesired microorganisms of the natural microflora of the skin e.g. corynebacterium acnes, propionibacte ⁇ um acnes, corynebacterium xerosis.
  • the inhibition of the growth of microorganisms of the natural microflora of the skin e.g. staphylococcus epiderimidis
  • ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇
  • Microorganisms in the sense of the present invention are for example bacteria (gram positive and gram-negative bacteria), yeasts, fungi and viruses, preferably bacteria, yeasts or fungi.
  • microorganisms described herein are microorganisms selected from for example Staphylococci, Micrococci, Escherichia, Pseudomonas, Bacilli, Salmonella, Shigella, Porphyromonas, Prevotella, Wolinella, Campylobacter, Propionibacterium, Streptococci, Corynebacterium, Treponema, Fusobacte ⁇ um, Bifidobacterium, Lactobacillus, Actinomyces, Candida, Malazessia, Aspergillus, herpes simplex 1 and 2.
  • the ionic liquids according to the present invention show a good microbiocidal activity, that means the number of germs in a medium can be reproducibly decreased.
  • the number of microorganisms can be decreased to zero over a time period of 3 hours (starting with an inokulum of ca. 10 5 microorganisms/ml and a verum test concentration of 1%).
  • Even yeasts and fungi could be eliminated within that time frame or even faster
  • the antimicrobial activity of the compositions according to the present invention can be shown by tests known for a person skilled in the art, for example those based on DIN 58940 and 58944.
  • the ionic liquids of formula I are especially useful as disinfectants in human hygiene biocidal products, as private area and public health area disinfectans , in veterinary hygiene biocidal products, as food and feed area disinfectans and as drinking water disinfectants or as preservatives like in- can preservatives, film preservatives, wood preservatives, fibre, leather, rubber and polymerized materials preservatives, masonry preservatives, preservatives for liquid-cooling and processing systems, slimicides, preservatives for food or feedstocks or preservatives for cosmetics.
  • the invention relates likewise to a composition comprising at least one compound of formula I as described above.
  • compositions according to the present invention can be used in the form of solutions, suspensions, emulsions, pastes, ointments, gels, creams, lotions, powders, oils, waxes, pencils, shampoos, deodorants-creames, gels, deodorant sticks, roll-ons, aerosols, sprays, pump sprays or lacquers.
  • compositions of the invention may be in the form of cosmetic formulations, medicinal products, paints, inks, home care products, animal care products, products for personal and work hygiene, contact lenses, chromatography materials, medical equipment, protective topicals, lacquers, textiles, coatings and/or plastics.
  • Diagnosis monitoring, treatment, alleviation of or compensation for an injury or handicap.
  • formulations can mean for example antimicrobial cleansers, soaps, anti-fouling and antimicrobial paints for inside and outside use, antimicrobial wallpapers, antimicrobial dressings and plasters, prostheses and bone cement with antimicrobial activity, dental fillings, dental prostheses, formulations against gastrointestinal infections, active coal, antimicrobial cat litter, antimicrobial diapers, tampons or sanitary towels, ambient fragrances for rooms or cars, formulations for oral or body care, absorbent pads, air conditioning (filters and ducts), air inflated construction (air halls), agricultural and mulch films,
  • compositions according to the invention may include or comprise, essentially consist of or consist of the said necessary or optional constituents. All compounds or components which can be used in the agents or compositions are either known and commercially available or can be synthesised by known processes.
  • the invention likewise relates to a process for the preparation of a composition as described above, characterised in that at least one compound of formula I as described above is mixed with a carrier and optionally with further active compounds or auxiliaries.
  • the carriers and optionally the further active compounds or auxiliaries depends on the application field of the inventive composition and are known to the skilled artisan in said field of application.
  • the composition comprising at least one compound of formula I according to the present invention is a cosmetic formulation.
  • Cosmetic formulations can be in the form of solutions, suspensions, emulsions, pastes, ointments, gels, creams, lotions, powders, oils, waxes, pencils, shampoos, deodorants-creames, gels, lotions, emulsions, deodorant sticks, roll-ons, aerosols, sprays, pump sprays or lacquers, especially nail lacquers.
  • the antimicrobial activity of the compositions according to the present invention can advantageously be used.
  • the antimicrobial activity is of great importance due to rapid fouling and contamination with bacteria of materials in these application areas.
  • the amount of at least one compound of formula I is not crucial per se and can be adapted in each case to obtain the most effective result.
  • the content preferably lies in the range of 0.005% to 100% per weight, based on the composition in total. (100% if used as pure ionic liquid for cleaining surface areas etc.).
  • the content preferably lies in the range of 0.005% to 2% per weight, preferably in the range of 0.01 to 1% per weight, particularly preferably in the range of 0.02% to 0.5% per weight, based on the composition in total.
  • compositions according to the present invention can advantageously be combined with all known preservatives or antimicrobial agents, such as for example phenoxyethanol, triclosan, 7-ethylbicyclooxazolidine, benzoic acid, bronopol, butylparaben, chlorphenesin, diazolidinyl urea, dichlorobenzyl alcohol, dimethyl oxazolidine, DMDM hydantoin, ethylparaben, hexamidine diisethionate, imidiazolidinyl urea, imidiazolidinyl urea NF, iodopropynyl butylcarbamate, isobutylparaben, methylparaben, potassium sorbate NF FCC, propylparaben, quaternium-15, sodium benzoate NF FCC, sodium caprylate, sodium dehydroacetate, sodium dehydroacetate FCC 1 sodium
  • Poloxamer 188 PVP-lodine, Rosmarinus officinalis Leaf extract, Vitis vinifera seed extract, ammomium benzoate, ammonium propionate, 5- bromo-5-nitro-1 ,3-dioxane, chloroxylenol, ethyl alcohol, glutaral, iodopropynyl butylcarabamate, isothiazolinone, parabens, pircotone olamine, selenium disulphine, sorbic acid, zinc pyrithione, dehydroacetic acid, dimethyl hydroxmethyl pyrazole, formaldehyde, hexetidine, methyldibromo glutaronitrile, salicylic acid, sodium iodate, zinc oxide, benzyl alcohol, boric acid, chloroacetamide, phenoxythanol, ortholphenylphenol, 7-ethyl bicycloxazolidine, imidazolidinyl urea,
  • Hydantoin Stearate Phenol, , Phenoxyethylparaben, Phenoxyisopropanol, Phenyl Benzoate, Phenyl Mercuric Acetate, Phenyl Mercuric Benzoate, Phenyl Mercuric Borate, Phenyl Mercuric Bromide, Phenyl Mercuric Chloride, Phenylparaben, o-Phenylphenol, Polyaminopropyl Biguanide Stearate, Polyquaternium-42; Potassium Benzoate, Potassium
  • Methylparaben/ethylparaben/butylparaben/propylparaben/1 ,3-butylene glycol isomer Methylparaben/propylparaben, Methylparaben/propylparaben/benzyl alcohol,
  • Methylparaben/propylparaben/bronopol/phenoxyethanol Methylparaben/propylparaben/bronopol/propylene glycol
  • Methylparaben/propylparaben/ethylparaben Methylparaben/propylparaben/propylene glycol/diazolidinyl urea
  • Phenoxyethanol/benzoic acid/dehydroacetic acid Phenoxyethanol/benzyl alcohol/potassium sorbate/tocopherol
  • Phenoxylethanol/chlorphenesin/glycerin/methylparaben/benzoic acid Phenoxyethanol/DMDMhydantoin/lodopropynyl butyl carbamate
  • Phenoxyethanol/DMDM hydantoin/methylparaben/propylparaben Phenoxyethanol/isopropylparaben/isobutylparaben/butylparaben,
  • Phenoxyethanol/methyldibromo glutaronitrile/idopropynyl butylcarbamate Phenoxyethanol/methylparaben/butylparaben/ethylparaben/propylparaben, Phenoxyethanol/methylparaben/butylparaben/ethylparaben/propylparaben/i sobutyl-paraben, Phenoxyethanol/methylparaben/isobutylparaben/butylparaben,
  • the combination of compounds of formula I according to the present invention with preservatives or antimicrobial agents shown above may help to boost the antimicrobial performance of the preservative or antimicrobial agent in a formulation. This may even allow to decrease the amount of the preservative or antimicrobial agent in formulations or applications, thus avoiding or decreasing undesired effects that are associated with the use of said preservative or antimicrobial agent such as adverse effects to skin, hair or the environment.
  • antibiotics in this sense mean all known antibiotics, for example selected from the group of Beta-lactam, Vancomycin, Macrolides, Tetracyclines, Quinolones, Fluoroquinolones, Nitrated compounds (as for instance Nitroxoline, Tilboquinol or Nitrofurantoin), Aminoglycosides, Phenicols, Lincosamids, Synergistins, Fosfomycin, Fusidic acid, oxazolidinones, Rifamycins, Polymixynes, Gramicidins, Tyrocydine, Glycopeptides, Sulfonamides or Trimethoprims.
  • Antibiotics in this sense mean all known antibiotics, for example selected from the group of Beta-lactam, Vancomycin, Macrolides, Tetracyclines, Quinolones, Fluoroquinolones, Nitrated compounds (as for instance Nitroxoline, Tilboquinol or Nitrofurantoin), Amin
  • Combinations of compositions and antibiotics are advantageous with respect to the resistance of several microorganisms against certain antibiotics.
  • a combination of antibiotics with compositions according to the present invention helps to overcome the resistance by simply decreasing the number of microorganisms, which have not been affected by the antibiotics.
  • the antimicrobial activity can be useful in several stages of the processing.
  • plastics or polymers comprising compounds of formula I according to the present invention can be stored in the form of Masterbatches for a long period of time, without risking the contamination of the Masterbatch with microorganisms.
  • Masterbatch can be processed in the same way as all known Masterbatches.
  • the therewith-obtained products are useful in building and construction, household, items and furnishing, electrical and electronics parts, apparel, textiles and fabrics, coatings and laminates, transportation and recreation, adhesives, sealants and grouts, food contact items and water contact items, such as for example plastic bottles, bottle caps, films, coextrusion films, exterior and interior automotive parts etc, having surfaces, which again show antimicrobial activity.
  • bottles and films comprising compositions according to the present invention are of interest with respect to the decrease of the number of microorganisms in therein-packaged products and consumer goods.
  • plastics or polymers used in baths, swimming pools, kitchens, joints compounds, sealing compounds or in other generally humid surroundings can advantageously be provided with compositions according to the present invention.
  • Suitable plastics and polymers from which the articles are fabricated include synthetic, natural and semisynthetic organic polymers.
  • Example of polymers that can be used to practice this invention include, but are not limited to, aliphatic and aromatic polyesters, including polyethylene terephthalate, polybutylene terephthalate, polyethylene isophthalate, polyhexamethylene terephthalate, polylactic acid, polyglycolic acid, and liquid crystalline polymers for high performance resins and fibers; polyester block copolymers; aliphatic and aromatic polyamides including nylon 6, nylon 66, nylon 610, nylon 11 , nylon 12, nylon 1212, poly-p-phenylene terephthalamide, poly-m-phenylene isophthalamide; copolymerised polyamides; polyolefins including polyethylene, polypropylene, and copolymers thereof; vinyl polymers, including polystyrene, polyacrylonitrile, polyvinylalcohol, polyvinyl acetate, polyvinylchloride, polyvinylidene chloride, ABS resins and acrylic resins; copolymers of ethylene and vinyl
  • polyvinylidene fluoride and polyvinyl fluoride polyurethanes; segmented polyurethane elastomers, spandex or elastane elastomers; polyethers, including polyacetals; polyketones, polyetherether ketone (PEEK), polyether ketoneketone (PEKK); polyether and polyester block polymers; polysulfides; polysulfones: polysiloxanes such as polydimethyl siloxane; polycarbonates; thermosetting synthetic polymers such as phenol-formaldehyde copolymer, polyurethane, polyesterurethane, polyetherurethane, polyetherurethaneurea, polyesterurethaneurea; natural polymers such as cellulosics, cotton and wool; and regenerated or semi-synthetic polymers such as rayon, cuprammonium rayon, acetate rayon, triacetate rayon, reconstituted silk and polysaccharides.
  • PEEK polyetherether ketone
  • Spandex is defined herein to refer to a fiber or filament made from a long chain synthetic polymer that comprises at least 85 % by weight of segmented polyurethane.
  • the polymer articles of this invention can be, for example, in the shape of films, fibers, powders, granules or articles made there from such as containers, pipes and monofilaments for brushes.
  • the molded article preferably has a large surface area.
  • a polymer article of the present invention having antimicrobial properties is comprised of at least one compound of formula I and at least one organic polymer.
  • the polymer articles according to the present invention may contain other additives as well. They may contain, for example, polymerization catalysts, stabilizers, delustering agents, optical whitening agents, organic or inorganic pigments, inorganic fillers, plasticizers and so on. Examples of plastics which can be used here as well as preparation and processing methods can be found in RD 472005 or R. Glausch, M. Kieser, R. Maisch, G. Pfaff, J. Weitzel, Perlglanzpigmente, Curt R. Vincentz Verlag, 1996, 83 ff.
  • Paints and lacquers comprising compounds of formula I according to the present invention can be waterborne or solvent-based. They can be on the basis of synthetic or chemically modified natural polymers, such as for example, acryl polymers, vinyl polymers, alkyd resins, phenol resins, urea resins, melamine resins, polyester resins, cellulose nitrate, epoxy resins polyurethane resins, bitumen, tar, shellac, natural rubber or resins, and can comprise all known additives and adjuvants, such as for example sikkatives, waxes, dispersing agents, anti-blocking agents or drying agents.
  • synthetic or chemically modified natural polymers such as for example, acryl polymers, vinyl polymers, alkyd resins, phenol resins, urea resins, melamine resins, polyester resins, cellulose nitrate, epoxy resins polyurethane resins, bitumen, tar, shellac, natural rubber or resins.
  • Paints and lacquers provided with compositions can be used for example in the automotive area or in the industrial area, in powder coatings, architectural use, as coating of wood, steel, inner walls, floors, blankets, facades or in humid surroundings thus providing the surfaces antimicrobial activity. Furthermore the coating is stabilized against attacks of microorganisms thus enhancing the durability of the coatings.
  • Compounds of formula I or compositions comprising compounds of formula I according to the present invention can advantageously be applied to all kinds of printing inks, such as liquid inks, UV curable inks, paste inks and paper coatings.
  • Known preparations for these appliation areas lack sufficient stability against antimicrobial contamination, especially in water based systems.
  • the usage of compounds or compositions according to the present invention can help to minimize the contamination with microorganisms thus allowing to decrease the necessary content of preservatives.
  • the therewith provided preparations are stable for a long period of time.
  • the liquid inks can be water based, based on water/alcohol mixtures or solvent based.
  • Suitable binders for aqueous inks are acrylates, methacrylates, polyesters and polyurethanes.
  • Binders for solvent based inks are nitrocellulose, ethylcellulose, polyamide, PVC/PVA-copolymers, polyvinylbutyrale, clorinated rubber, rosin modified phenolic resins, maleinic resins, calcium/zinc-resinate-EHEC, acrylates and mixtures thereof.
  • Solvents which can be used in solvent based inks are ethanol, isopropanol, n-propanol, aceton, ethylacetate, isopropylacetate, n-propylacetate, methoxypropanol, ethoxypropanol, toluene, aliphatic hydrocarbons and mixtures.
  • UV-curable printing inks are basically composed of a binder and a liquid monomer, such as epoxy acrylates, polyurethane acrylates, polyester acrylates as reactive monomers hexanediol diacrylate, di/tripropyleneglycol diacrylate, trimethylpropane triacrylate, trimethylolpropaneethoxy triacrylate and mixtures thereof.
  • a liquid monomer such as epoxy acrylates, polyurethane acrylates, polyester acrylates as reactive monomers hexanediol diacrylate, di/tripropyleneglycol diacrylate, trimethylpropane triacrylate, trimethylolpropaneethoxy triacrylate and mixtures thereof.
  • Paste inks containing compounds according to the present invention can further contain rosin modified phenolic resins, maleinic acid modified resins, alkyd resins, linseed/soibean oil based resins, hydrocarbon based resins and mineral oils, linseed oil or soybean oil as solvents.
  • Paper coatings containing antimicrobial compounds may further contain starch, protein/casein, polyvinyl alcohol, latexes, carboxymethyl cellulose or acrylate binders.
  • the printing inks may further contain known fillers and rheology modifiers. More information on technology and compositions of printing inks is provided by R. L. Leach, R. J. Pierce, in The Printing Ink Manual, Fifth Edition, Blueprint, London, 1993.
  • deodorants may be a special form of cosmetic formulations according to the present invention. Different forms of deodorants are in mind: deodorant-cremes, gels, lotions, emulsions, deodorant sticks, RoII- ons, sprays and pump sprays.
  • the compounds of formula I are combined with a suitable carrier material used in deodorants.
  • suitable carrier materials are glyceryl stearate, aluminium chlorohydrate, propylene glycol, carbomer, glycerin, dicapryl ether, ethanol, glyceryl cocoate, cylomethicone, dimethicone, dipropylene glycol, stearyl alcohol, mineral oil, phenyltrimethicone or sodium stearate.
  • the odour production of the skin is the result from the modifications of initially odourless secretions from the apocrine glands, such as for example lipids, proteins, ammonia, steroids and reducing sugars, by microorganisms, like for example Staphylococcus, Corynebacterium or malassezia.
  • the inventive compounds of formula I are effective against the Gram-positive cocci group, for example against the Micrococcaceae family (Staphylococcus aureus, staphylococcus epidermidis, staphylococcus hominis), against the Gram-positive rods, for example against the Coryneforms family (Brevibacterium and /or corynebacterium for example) causing malodour of the skin, which can be reduced by deodorants comprising these compounds of formula I.
  • the deodorants may comprise various adjuvants used in this type of composition, such as scents or perfumes, other preservatives, electrolytes, silicone derivatives, dyes and/or pigments which colour the composition itself, or other ingredients customarily used for deodorants. Further ingredients that can be incorporated into the formulations are described later in this application in more detail.
  • compositions according to the present invention can also be used for oral care, for example for prophylaxis and/or treatment of dental plaque, caries or oral malodour.
  • oral malodour, caries and dental plaque are caused by microorganisms, for example by Streptococcus sobrinus, Streptococcus mutans, Streptococcus gordonii, Streptococcus salivaris, Streptococcus sanguis, Actinomyces, Lactobacilli, Fusobacterium, Veillonella, Treponema, denticola, Porphyromonas. gingivalis, Bacteroides or Peptostreptococcus.
  • the oral composition may be formulated for use in any form of interdental or periodontal treatment and may be in the form, for example, of a dentifrice, mouthwash, toothpowder, chewing gum, lozenge, mouth spray, floss, dental paint, or glass ionomer cement.
  • Use of the antimicrobial material of the present invention in a glass ionomer cement has the advantage of providing X-ray opacity as well as antimicrobial action.
  • compositions may, as appropriate, contain conventional materials such as, for example, humectants, surfactants, gelling agents, abrasives or low abrasive spheres, fluoride sources, desensitizing agents, flavorings, colorings, sweeteners, preservatives, structuring agents, bactericides, anti- tartar agents and anti-plaque agents.
  • conventional materials such as, for example, humectants, surfactants, gelling agents, abrasives or low abrasive spheres, fluoride sources, desensitizing agents, flavorings, colorings, sweeteners, preservatives, structuring agents, bactericides, anti- tartar agents and anti-plaque agents.
  • Suitable humectants for use in dentifrice compositions include polyhydric alcohols such as xylitol, sorbitol, glycerol, propylene glycol and polyethylene glycols. Mixtures of glycerol and sorbitol are particularly effective.
  • a humectant helps to prevent dentifrice compositions from hardening on exposure to air, and may also provide a moist feel, smooth texture, flowability, and a desirable sweetness in the mouth.
  • such humectants may comprise from about 0% - 85 %, preferably from about 0% - 60 % by weight of the oral hygiene composition.
  • compositions comprising at least one compound of formula I according to the present invention usually comprise several ingredients.
  • ingredients especially for cosmetic formulations, are given.
  • Preferred formulations or applications additionally comprise at least one insect repellent, preferably selected from the group ethyl 3-(N-n-butyl-N- acetylamino)propionate, 2-(2-hydroxyethyl)-1 -methylpropyl 1 -piperidine- carboxylate, N,N-diethyl-3-methylbenzamide, dimethyl phthalate, butopyro- noxyl, 2,3,4,5-bis(2-butylene)tetrahydro-2-furaldehyde, N,N-diethylcapryl- amide, N,N-diethylbenzamide, o-chloro-N.N-diethylbenzamide, dimethyl carbate, di-n-propyl isocinchomeronate, 2-ethylhexane-1 ,3-diol, N-octylbi- cycloheptenedicarboximide or piperonyl butoxide, particularly preferably selected from the group 3-
  • Preferred formulations or applications additionally comprise at least one UV filter resulting in antimicrobial preparations having light protection properties.
  • the UV filter can preferably be selected from the group of dibenzoylmethane derivatives.
  • the dibenzoylmethane derivatives used within the scope of the present invention are products which are already well known per se and are described, in particular, in the specifications FR- A-2 326 405, FR-A-2 440 933 and EP-A-O 114 607.
  • UV filters are suitable for combination with dibenzoylmethane derivatives and with the compounds of the formula I according to the invention, for example one or more additional hydrophilic or lipophilic sun-protection filters which are effective in the UV-A region and/or UV-B region and/or IR and/or VIS region (absorbers).
  • additional filters can be selected, in particular, from cinnamic acid derivatives, salicylic acid derivatives, camphor derivatives, triazine derivatives, ⁇ , ⁇ -diphenyl acrylate derivatives, p-aminobenzoic acid derivatives and polymeric filters and silicone filters, which are described in the application WO 93/04665.
  • Further examples of organic filters are indicated in Patent Application EP-A 0 487 404. Particular preference is given to UV filters whose physiological acceptability has already been demonstrated. Both for UVA and UVB filters, there are many proven substances which are known from the specialist literature.
  • organic UV filters are generally incorporated into cosmetic formulations in an amount of from 0.5% to 10% by weight, preferably 1% - 8% by weight, based on the composition in total. It may furthermore be preferred in accordance with the invention for the preparations to comprise further inorganic UV filters. Preference is given here both to those from the group consisting of titanium dioxides, such as, for example, coated titanium dioxide (for example Eusolex® T-2000 or Eusolex ® T-AQUA), zinc oxides (for example Sachtotec®), iron oxides and also cerium oxides.
  • These inorganic UV filters are generally incorporated into cosmetic preparations in an amount of from 0.5% to 20% by weight, preferably 2% - 10% by weight, based on the compositin in total. In particular, it may be preferred here for a UV-Filter to be incorporated into one phase of emulsions and a further inorganic UV filter to be incorporated into the other phase.
  • compounds of formula I according to the present invention with antioxidants, humectants, vitamins such as panthenol, or vitamin B6 derivatives (e.g. niacin amide) or any derivative of ascorbic acid, skin and hair care actives, in particular watersoluble actives such as carnitine, creatinine, creatine, ectoin, dihydroxyacetone, quaternized actives, and bioflavanoids such as troxerutin or isoquercetin_or
  • UV filters like phenyl benzimidazole sulfonic acid
  • Preferred auxiliaries originate from the group consisting of stabilisers, solubilisers, colorants and odour improvers.
  • Ointments, pastes, creams and gels may comprise the customary excipi- ents, for example animal and vegetable fats, waxes, paraffins, starch, tra- gacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc and zinc oxide, or mixtures of these substances.
  • customary excipi- ents for example animal and vegetable fats, waxes, paraffins, starch, tra- gacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc and zinc oxide, or mixtures of these substances.
  • Powders and sprays may comprise the customary excipients, for example lactose, talc, silica, aluminium hydroxide, calcium silicate and polyamide powder, or mixtures of these substances.
  • Sprays may additionally comprise the customary propellants, for example chlorofluorocarbons, propane/butane or dimethyl ether.
  • Solutions and emulsions may comprise the customary excipients, such as solvents, solubilisers and emulsifiers, for example water, ethanol, isopro- panol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butyl glycol, oils, in particular cottonseed oil, peanut oil, wheatgerm oil, olive oil, castor oil and sesame oil, glycerol fatty acid esters, polyethylene glycols and fatty acid esters of sorbitan, or mixtures of these substances.
  • solvents such as solvents, solubilisers and emulsifiers
  • solvents such as solvents, solubilisers and emulsifiers
  • solvents such as solvents, solubilisers and emulsifiers
  • solvents such as solvents, solubilisers and emulsifiers
  • solvents such as solvents
  • Suspensions may comprise the customary excipients, such as liquid dilu- ents, for example water, ethanol or propylene glycol, suspending agents, for example ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminium metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances.
  • liquid dilu- ents for example water, ethanol or propylene glycol
  • suspending agents for example ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminium metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances.
  • Soaps may comprise the customary excipients, such as alkali metal salts of fatty acids, salts of fatty acid monoesters, fatty acid protein hydrolysates, isethionates, lanolin, fatty alcohol, vegetable oils, plant extracts, glycerol, sugars, or mixtures of these substances.
  • Surfactant-containing cleansing products can comprise the conventional carriers, such as salts of fatty alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic acid monoesters, fatty acid albumen hydrolysates, isothionates, imidazolinium derivatives, methyl taurates, sarcosinates, fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable and synthetic oils, lanolin derivatives, ethoxylated glycerol fatty acid esters or mixtures of these substances.
  • conventional carriers such as salts of fatty alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic acid monoesters, fatty acid albumen hydrolysates, isothionates, imidazolinium derivatives, methyl taurates, sarcosinates, fatty acid
  • Face and body oils may comprise the customary excipients, such as synthetic oils, such as fatty acid esters, fatty alcohols, silicone oils, natural oils, such as vegetable oils and oily plant extracts, paraffin oils or lanolin oils, or mixtures of these substances.
  • synthetic oils such as fatty acid esters, fatty alcohols, silicone oils, natural oils, such as vegetable oils and oily plant extracts, paraffin oils or lanolin oils, or mixtures of these substances.
  • the preferred preparation forms according to the invention include, in particular, emulsions.
  • the aqueous phase of the preparations according to the invention optionally advantageously comprises alcohols, diols or polyols having a low carbon number, and ethers thereof, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene glycol monomethyl or monoethyl ether and analogous products, furthermore alcohols having a low carbon number, for example ethanol, isopropanol, 1 ,2-propanediol or glycerol, and, in particular, one or more thickeners, which may advantageously be selected from the group consisting of silicon dioxide, aluminium silicates, polysaccharides and deriva- tives thereof, for example hyaluronic acid, xanthan gum, hydroxypropyl- methylcellulose, particularly advantageously from the group consisting of the
  • Cosmetic and dermatological preparations according to the invention may exist in various forms. Thus, they may be, for example, a solution, a water- free preparation, an emulsion or microemulsion of the water-in-oil (W/O) or oil-in-water (O/W) type, a multiple emulsion, for example of the water-in-oil- in-water (W/O/W) type, a gel, a solid stick, an ointment or an aerosol. It is also advantageous to administer ectoins in encapsulated form, for example in collagen matrices and other conventional encapsulation materials, for example as cellulose encapsulations, in gelatine, wax matrices or liposo- mally encapsulated. In particular, wax matrices, as described in DE-A
  • Emulsions, W/O emulsions and O/W emulsions are obtainable in a conventional manner.
  • Emulsifiers that can be used are, for example, the known W/O and O/W emulsifiers. It is advantageous to use further conventional co-emulsifiers in the preferred O/W emulsions according to the invention.
  • the commercially available product Ceralution C (Sasol) has to be proven to be in particular advantageous as emulsifier.
  • Co-emulsifiers which are advantageous according to the invention are, for example, O/W emulsifiers, principally from the group consisting of the substances having HLB values of 11-16, very particularly advantageously having HLB values of 14.5-15.5, so long as the O/W emulsifiers have satu- rated radicals R and R'. If the O/W emulsifiers have unsaturated radicals R and/or R' or in the case of isoalkyl derivatives, the preferred HLB value of such emulsifiers may also be lower or higher.
  • the preparation may comprise cosmetic adjuvants which are usually used in this type of preparation, such as, for example, thickeners, softeners, moisturisers, surface-active agents, emulsifiers, preservatives, antifoams, perfumes, waxes, lanolin, propellants, dyes and/or pigments which colour the composition itself or the skin, and other ingredients usually used in cosmetics.
  • cosmetic adjuvants which are usually used in this type of preparation, such as, for example, thickeners, softeners, moisturisers, surface-active agents, emulsifiers, preservatives, antifoams, perfumes, waxes, lanolin, propellants, dyes and/or pigments which colour the composition itself or the skin, and other ingredients usually used in cosmetics.
  • Emulsions according to the invention are advantageous and comprise, for example, the said fats, oils, waxes and other fatty substances, as well as water and an emulsifier, as usually used for a preparation of this type.
  • oils such as triglycerides of capric or caprylic acid, furthermore natural oils, such as, for example, castor oil;
  • esters of fatty acids with alcohols having a low carbon number for example with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with alkanoic acids having a low carbon number or with fatty acids;
  • silicone oils such as dimethyipolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms thereof.
  • the oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions is advantageously selected from the group consisting of esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 3 to 30 carbon atoms and saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of from 3 to 30 carbon atoms, or from the group consisting of esters of aromatic carboxylic acids and saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of from 3 to 30 carbon atoms.
  • Ester oils of this type can then advantageously be selected from the group consisting of isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, 2-octyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyl oleate, erucyl erucate and synthetic, semi-synthetic and natural mixtures of esters of this type, for example jojoba oil.
  • the oil phase may furthermore advantageously be selected from the group consisting of branched and unbranched hydrocarbons and waxes, silicone oils, dialkyl ethers, or the group consisting of saturated and unsaturated, branched and unbranched alcohols, and fatty acid triglycerides, specifically the triglycerol esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 8 to 24, in particular 12-18, carbon atoms.
  • the fatty acid triglycerides may advantageously be selected, for example, from the group consisting of synthetic, semi-synthetic and natural oils, for example olive oil, sunflower oil, soya oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil and the like.
  • any desired mixtures of oil and wax components of this type may also advantageously be employed for the purposes of the present invention. It may also be advantageous to employ waxes, for example cetyl palmitate, as the only lipid component of the oil phase.
  • the invention therefore relates likewise to the use of said compounds as antibiotics and to the substances
  • these three related compounds as stated above falls in the definition of being an ionic liquid. Therefore these three related compounds may be used as solvent or solvent additive, as phase-transfer catalyst, as extractant, as heat-transfer medium, as surface-active substance, as plasticiser, as flame retardant, as conductive salt or additive in electrochemical cells as described above.
  • solvents for carbohydrate containing solids in particular biopolymers and derivatives or degredation products thereof are solvents for carbohydrate containing solids in particular biopolymers and derivatives or degredation products thereof.
  • these compounds can be applied as lubricants, working fluids for maschines, such as compressors, pumps or hydraulic devices.
  • These ionic liquids according to this invention may be also used in electro-chemical cells in particular for electo-optical cells or as functional materials in sensors.
  • the most preferred use of these three ionic liquids is the use as antibiotic against, preferably as antibiotic against staphylococcus epidermidis and pseudomonas aeruginosa..
  • the invention likewise relates to a process for the production of N-ethyl-
  • anion exchanger III 0.72 kg anion exchanger III is washed with water in a type G3 glass filter and dried. Afterwards, a solution of 120 g N-ethyl, N,N-dimethyl-2-hydroxy- ethylammonium bromide in 500 ml water is added. The pH of the solution after ion exchange is about pH 14. The content of bromide is about 51 mg/L.
  • an aqueous solution of N-ethyl-N,N-dimethyl-2- hydroxyethylammonium hydroxide (225 ml) is reacted with 11 ml propionic acid. After distillation of the solvent, 28 g N-ethyl-N,N-dimethyl-2-hydroxy- ethylammonium propionate of a clear liquid is obtained.
  • an aqueous solution of N-ethyl-N,N-dimethyl-2- hydroxyethylammonium hydroxide (225 ml) is reacted with 23 ml octanoic acid. After distillation of the solvent, 47 g N-ethyl-N,N-dimethyl-2-hydroxy- ethylammonium octanonate of a clear liquid is obtained.
  • reaction composition is mixed with 2,5 L ethylacetate and the product is precipitated. After separation and drying, 343 g of a white solid is obtained.
  • the aqueous solution of N-ethyl-N,N-dimethyl-2- methoxyethylammonium hydroxide is reacted with 22 ml of acetic acid. After distillation of the solvent, a clear liquid is obtained.
  • the aqueous solution of N-ethyl-N,N-dimethyl-2- methoxyethylammonium hydroxide is reacted with 26 ml of octanoic acid. After distillation of the solvent, 46 g of a clear liquid N-ethyl-N,N-dimethyl-2- methoxyethylammonium octanonate is obtained.
  • the challenge testing procedure consists in challenging a non- contaminated antimicrobial product according to the invention with a prescribed inoculum of suitable microorganisms and storing the inoculated product at a prescribed temperature, e.g. room temperature. The number of organisms surviving in the test products is determined at specified intervals of time.
  • a fresh stock culture of the specific micro-organsisms is inoculated on the surface of Agar medium B for bacteria and on the surface of Agar medium C for fungi.
  • the bacteria culture will be incubated until sufficient sporulation (18-24h at 30-35 0 C)
  • the surface of the Agar media is washed out with a sterile solution containing sodium chloride (9 g/l) and poured into an adequate vessel.
  • the concentration of germs in the suspension will be adjusted with the same solution to a concentration close to 10 8 micro-organism/ ml.
  • a sample of this suspension is taken and the germ concentration in CFU/ml will be measured using the method of membran filtration or counting on Agar plate. This determines the value of the inoculum.
  • the suspension must be used immediately.
  • the inoculated volume should not be above 1% v/v of the overall test solution.
  • the suspension will be mixed in order to get a good homogenisation.
  • the inoculated preparation is stored away from the daylight at 20-25 0 C.
  • 1 g or 1 ml samples from the tests preparation (containing the inoculated micro-organsisms and the antimicrobial product according to the invention) will be taken at different intervals of time (in our case , 0, 2 min, 5 min, 30 min, 1h, 3h, 6h, 24h, 48h, 7 days, 14 days and 28 days) and the number of microorganisms will be measured using the Agar plate or the membrane filtration method. It is important to make sure that any remaining antimicrobial activity to be eliminated by dilution, filtration or specific inactivation.
  • N-ethyl-N,N-dimethyl-2-methoxyethylammonium octanoate 1137
  • N-ethyl-N,N-dimethyl-2-hydroxyethylammonium octanoate 1132
  • N-ethyl-N,N-dimethyl-2-methoxyethylammonium acetate 1135
  • N-ethyl-N,N-dimethyl-2-hydroxyethylammonium acetate 1130
  • N-ethyl-N,N-dimethyl-2-hydroxyethylammonium propionate 1131
  • the above formulation A or B may of course contain one or more actives among the following list: Triethyl Citrate, Aluminium Chlorohydrate, Ethylhexylglycerol, Farnesol, Polyaminopropyl Biguanide, Aluminium Circonium .Tetrachlorohydrex GLY, Pentetic Acid, Diisopropylamine Aminoethylpropanol, Zinc Ricinoleate, aluminium salts, Lactic Acid, Triclosan.
  • phase A will be mixed at room temperature.
  • Phase B will be mixed at room temperature and will be given to phase A while stirring.
  • the above formulation may of course contain one or more actives among the following list: Myrtrimonium Bromid, Lactic Acid, Chlorohexidine Digluconate, Salicylic Acid, Phenoxyisopropanol, Isopropanol, Farnesol, Glycolic Acid, Tannic acid, Sulfur, Alcohol, Triclosan, Zinc Gluconate, Zinc PCA, Camphor, Aluminium salts, Sodium Lactate, Polyaminopropyl Biguanide, Zinc Acetat.
  • actives among the following list: Myrtrimonium Bromid, Lactic Acid, Chlorohexidine Digluconate, Salicylic Acid, Phenoxyisopropanol, Isopropanol, Farnesol, Glycolic Acid, Tannic acid, Sulfur, Alcohol, Triclosan, Zinc Gluconate, Zinc PCA, Camphor, Aluminium salts, Sodium Lactate, Polyaminopropyl Biguanide, Zinc Acetat.
  • Phase B is given to phase A while stirring.
  • Phase C is mixed and added to the combined phases A and B. Stirring until homogeneity.
  • the above formulation may of course contain one or more actives among the following list:
  • the above formulation may of course contain one or more actives among the following list:
  • Figure 1 Summary of results in log scale for 1132 and 1137 against
  • Figure 2 Summary of results in log scale for 1132 and 1137 against
  • Candida albicans Figure 3 Summary of results in log scale for 1132 and 1137 against

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Abstract

The present invention relates to special ammonium carboxylates, their synthesis and application, particularly as biocides.

Description

Ammoniumcarboxylates
The present invention relates to special ammonium carboxylates, their synthesis and their application, particularly as biocides.
Contamination of living organisms, like microbial, fungicidal or algicidal contamination is an essential concern in our daily life, whether it concerns cosmetic products, surface areas e.g. in bathrooms, hospitals or clean rooms, surgical instruments or wall paints. The usage of biocides is a common method for preventing contamination of living organisms.
A biocide is a chemical substance capable of killing living organisms, usually in a selective way. Biocides are commonly used in medicine, agriculture, forestry and in industry where they prevent e.g. the fouling of water and oil pipelines. Some substances used as biocides are also employed as anti-fouling agents or disinfectants under other circumstances. Biocides can be added to other materials or substrates, typically liquids, to protect them against biological infestation and growth.
The Biocidal Products Directive 98/8/EC (BPD), the classification of biocides, is broken down into 23 product types (i.e. application categories), with several comprising multiple subgroups. The four main groups are "disinfectants and general biocidal products", "preservatives", "pest control" and "other biocidal products" with the subgroups "preservatives for food or feedstocks", "antifouling products", "embalming and taxidermist fluids" and "control of other vertebrates".
However, many biocidal products are not well seen as such in view of their environmental behavior. Therefore, there is a real need of new biocides.
It is an object of the present invention to provide alternative biocides, especially as disinfectants or preservatives. Surprisingly it has been found that a special class of ammonium carboxylates are especially useful as biocides.
Therefore, the present invention is directed to compounds of formula I
[NRR1R2R3J+ [R4-COO]- I in which
R is alkoxymethyl or alkoxyethyl in which the alkoxy group is linear or branched and has 1 to 4 C atoms, hydroxy methyl, hydroxyethyl, hydroxypropyl or hydroxybutyl
R1 to R3 are independantly of each other linear or branched alkyl with 1 to 4 C atoms,
R4 is linear or branched alkyl with 5 to 11 C atoms, wherein the compound N,N,N-trimethyl-2-hydroxyethylammonium hexanoate is excluded.
N,N,N-Trimethyl-2-hydroxyethylammonium hexanoate is described as solvent for refined cork dissolution, particularly with respect to the separation of large quantities of suberin, in H. Garcia et al, Green Chem., 2010, 12, 367-369.
Additionally, compounds of formula I can be seen as ionic liquids or liquid salts. Typically, ionic liquids are ionic species which consist of an organic cation and a generally inorganic or organic anion. They preferably do not comprise neutral molecules and usually have melting points below 373 K. In the context of this patent application the term "ionic liquid" is used as a synonym to chemical compound or compound.
Compounds of formula I have unique properties which means they are water soluble, thermally stable, readily biodegradable and they are effective as biocides against various organisms as stated and documented in the examples. The linear or branched alkyl group with 1 to 4 C-atoms is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl or tert.-butyl.
The linear or branched alkyl group with 5 to 11 C-atoms is, for example, n- pentyl, methylbutyl, n-hexyl, ethylbutyl, methylpentyl, n-heptyl, n-octyl, ethylhexyl, n-nonyl, n-decyl or n-undecyl.
The linear or branched alkoxy group with 1 to 4 C-atoms is, for example, methoxy, ethoxy, isopropoxy, propoxy, butoxy, sec-butoxy or tert-butoxy.
The subsitutent R4 in formula I is preferably linear alkyl with 5 to 11 C- atoms, particularly preferably n-pentyl, n-hexyl, n-heptyl or n-undecyl, very particularly preferably n-heptyl.
The substituents R1 to R3 in the compounds of the formula I may be identical or different. Preferably two substituents are identical and one substituent is different.
The substituents R1 to R3 are independantly of each other preferably methyl or ethyl. Particularly preferably, two substituents of R1 to R3 are methyl and the other substituent is ethyl or two substituents of R1 to R3 are ethyl and the other substituent is methyl. Very particularly preferably, two substituents of R1 to R3 are methyl and the other substituent is ethyl.
The substituent R is preferably methoxyethyl, ethoxyethyl or hydroxyethyl.
Further preferred combinations are disclosed in the claims.
Preferred compounds of formula I are N-ethyl-N,N-dimethyl-2-methoxyethylammonium hexanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium hexanoate, N-ethyl-N,N-dimethyl-2-methoxyethylammonium octanoate, - A -
N-ethyl-N,N-dimethyl-2-methoxyethylammonium decanoate N-ethyl-N,N-dimethyl-2-methoxyethylammonium dodecanoate, N-ethyl-N,N-dimethyl-2-hydroxyethylammonium hexanoate, N-ethyl-N,N-dimethyl-3-hydroxypropylammonium hexanoate, N-ethyl-N,N-dimethyl-4-hydroxybutylammonium hexanoate,
N-ethyl-N,N-dimethyl-2-hydroxyethylammonium octanoate, N-ethyl-N,N-dimethyl-2-hydroxyethylammoniunn decanoate N-ethyl-N,N-dimethyl-2-hydroxyethylammonium dodecanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium hexanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium octanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium decanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium dodecanoate, N,N-diethyl-N -methyl-2-methoxyethylammonium hexanoate, N,N-diethyl-N -methyl-2-methoxyethylammonium octanoate, N,N-diethyl-N -methyl-2-methoxyethylammonium decanoate
N,N-diethyl-N -methyl-2-methoxyethylammonium dodecanoate, N,N-diethyl-N -methyl-2-hydroxyethylammonium hexanoate, N,N-diethyl-N -methyl-2-hydroxyethylammonium octanoate, N,N-diethyl-N -methyl-2-hydroxyethylammonium decanoate N,N-diethyl-N -methyl-2-hydroxyethylammoπium dodecanoate, N,N-diethyl-N -methyl-2-ethoxyethylammonium hexanoate, N,N-diethyl-N -methyl-2-ethoxyethylammonium octanoate, N,N-diethyl-N -methyl-2-ethoxyethylammonium decanoate, N,N-diethyl-N -methyl-2-ethoxyethylammonium dodecanoate, N,N,N-triethyl-2-ethoxyethylammonium hexanoate, N,N,N-triethyl-2-methoxyethylammonium hexanoate, N,N,N-triethyl-2-hydroxyethylammonium hexanoate, N,N,N-trimethyl-2-hydroxyethylammonium octanoate N-ethyl-N,N-dimethyl-2-ethoxyethylammonium heptanoate, N-ethyl-N,N-dimethyl-2-methoxyethylammonium heptanoate, N,N-diethyl-N-methyl-2-methoxyethylammonium heptanoate, N,N-diethyl-N-methyl-2-ethoxyethylammonium heptanoate, N,N,N-triethyl-2-ethoxyethylammonium heptanoate, N,N,N-triethyl-2-methoxyethylammonium heptanoate, N,N,N-trimethyl-2-ethoxyethylammonium heptanoate.
Particularly preferred compounds are
N-ethyl-N,N-dimethyl-2-methoxyethylammonium octanoate, N-ethyl-N,N-dimethyl-2-hydroxyethylammonium octanoate.
The invention likewise relates to a process for the production of compounds of formula I, as described above, in which ammonium halides of formula Il
[NRR1R2R3I+ [HaI]- II, in which Hal is Cl, Br or I and R, R1 to R3 has a meaning as described above, are converted to hydroxides via ion exchange followed by reaction with the acid R4-COOH, in which R4 has a meaning as described above.
The compounds of formula Il are commercially available or may be synthesized by methods which are described, for example, in the standard works, such as Houben-Weyl, Methoden der organischen Chemie [Methods of Organic Chemistry], Georg-Thieme-Verlag, Stuttgart, to be precise under reaction conditions which are known and suitable for the said reactions. Use can also be made here of variants known per se which are not mentioned here in greater detail.
As an example, the ammonium halides of formula Il may be synthesized by reaction of corresponding amines NRR1R2 with haloalkanes HaIR3 in solvents at temperatures between 10 and 1000C. Typical solvents are acetonitrile, isopropanol, toluene, heptane or cyclohexane. The reaction may also be carried out in the absence of a solvent or using an excess of one of the two reagents as the solvent. A typical ion exchange resin which can be used in the inventive process is Merck Product Nr. 104767 Ion Exchanger III (strongly basic anion exchanger, OH-Form) for Analysis. All other ion exchange resins which have the same or similar properties as this strongly basic anion exchanger can be used.
The ion exchange typically takes place using water as the solvent for the ammonium halide. Useful solvents other than water are methanol, ethanol, propanol, butanol, isopropanol and isobutanol. The corresponding solution of the ammonium hydroxide is reacted with R4COOH to form the compound of formula I. The substituents R, R1 to R4 have the meaning as described above.
However it is possible to synthesize the corresponding hydroxide via bipolar membrane electrodialysis or via metathesis reaction of ammonium halides with a metal hydroxide such as silver hydroxide, lead hydroxide, potassium hydroxide or sodium hydroxide and to react it with the corresponding acid.
The present invention furthermore relates to the use of the said ionic liquids of formula I as solvent or solvent additive, as phase-transfer catalyst, as extractant, as heat-transfer medium, as surface-active substance, as plasticiser, as flame retardant, as supporting electrolyte or additive in electrochemical cells.
In the case of the use of the said ionic liquids as solvents, these are suitable in any type of reaction known to the person skilled in the art, for example for transition-metal- or enzyme-catalysed reactions, such as, for example, hydroformylation reactions, oligomerisation reactions, esterifications or isomerisations, where the said list is not exhaustive.
On use as extractant, the ionic liquid can be employed to separate off reaction products, but also to separate off impurities, depending on the solubility of the respective component in the ionic liquid. In addition, the ionic liquids may also serve as separation media in the separation of a plurality of components, for example in the distillative separation of a plurality of components of a mixture.
Further possible applications are use as plasticiser in polymer materials, as flame retardant for a number of materials or applications, and as a supporting electrolyte or additive in various electrochemical cells and applications, for example in galvanic cells, in capacitors or in fuel cells.
Further fields of applications of the new chemical compounds, e.g. ionic liquids, according to this invention are solvents for carbohydrate containing solids in particular biopolymers and derivatives or degredation products thereof. In addition, these new compounds can be applied as lubricants, working fluids for maschines, such as compressors, pumps or hydraulic devices. The ionic liquids according to this invention may be also used in electro-chemical cells in particular for electro-optical cells or as functional materials in sensors.
The most preferred use of ionic liquids of formula I is the use as biocides as defined above.
The ionic liquids according to the present invention can be used for the inhibition of the growth and/or progeny of microorganisms preferably in order to preserve compositions. In specific e.g. for cosmetic applications it may be of particular interest to inhibit the growth of undesired microorganisms of the natural microflora of the skin (e.g. corynebacterium acnes, propionibacteήum acnes, corynebacterium xerosis). The inhibition of the growth of microorganisms of the natural microflora of the skin (e.g. staphylococcus epiderimidis) is of particular interest for people with a weak immune defense or to clean medical devices in hospitals. Depending on the individual antimicrobial activity of the substance this might inhibit or sooth irritation, inflammation, the formation of acne or the excretion of sebum. Directly or indirectly described substances might improve skin and hair conditions, reduce hair loss, show anti-aging properties or act as antioxidants against the harmfull effects caused by oxidants such as reactive oxygen species, and light (visible, UV, IR). Exemplary hair conditions include improvements in hair gloss, hair volume and elasticity, in the stability of natural and artificial hair colors and in the inhibition or camouflage of hair-greying. Exemplary skin conditions include the improvements in the skin barrier function, skin hydration, skin oxidation status as well as in the support of a wound healing process. Described substances may prevent undesired body odors by their antimicrobial activities against e.g. bacteria that decompose sweat . They may provide or boost pigmentation control activities on skin and hair such as tanning and lightening activities.
Microorganisms in the sense of the present invention are for example bacteria (gram positive and gram-negative bacteria), yeasts, fungi and viruses, preferably bacteria, yeasts or fungi. Examples of microorganisms described herein are microorganisms selected from for example Staphylococci, Micrococci, Escherichia, Pseudomonas, Bacilli, Salmonella, Shigella, Porphyromonas, Prevotella, Wolinella, Campylobacter, Propionibacterium, Streptococci, Corynebacterium, Treponema, Fusobacteήum, Bifidobacterium, Lactobacillus, Actinomyces, Candida, Malazessia, Aspergillus, herpes simplex 1 and 2.
The ionic liquids according to the present invention show a good microbiocidal activity, that means the number of germs in a medium can be reproducibly decreased. In particular the number of microorganisms can be decreased to zero over a time period of 3 hours (starting with an inokulum of ca. 105 microorganisms/ml and a verum test concentration of 1%). Even yeasts and fungi could be eliminated within that time frame or even faster The antimicrobial activity of the compositions according to the present invention can be shown by tests known for a person skilled in the art, for example those based on DIN 58940 and 58944.
Therefore, the ionic liquids of formula I are especially useful as disinfectants in human hygiene biocidal products, as private area and public health area disinfectans , in veterinary hygiene biocidal products, as food and feed area disinfectans and as drinking water disinfectants or as preservatives like in- can preservatives, film preservatives, wood preservatives, fibre, leather, rubber and polymerized materials preservatives, masonry preservatives, preservatives for liquid-cooling and processing systems, slimicides, preservatives for food or feedstocks or preservatives for cosmetics.
The invention relates likewise to a composition comprising at least one compound of formula I as described above.
Therefore, in a preferred embodiment of the invention compositions according to the present invention can be used in the form of solutions, suspensions, emulsions, pastes, ointments, gels, creams, lotions, powders, oils, waxes, pencils, shampoos, deodorants-creames, gels, deodorant sticks, roll-ons, aerosols, sprays, pump sprays or lacquers.
The compositions of the invention may be in the form of cosmetic formulations, medicinal products, paints, inks, home care products, animal care products, products for personal and work hygiene, contact lenses, chromatography materials, medical equipment, protective topicals, lacquers, textiles, coatings and/or plastics.
Within the following medicinal product shall mean a medical device as defined below. Directive 2007/47/ec of the European Parliament and of the council of 5 September, 2007, which amended the Council Directive 93/42/EEC of 14 June, 1993 concerning medical devices, defines a medical device as any instrument, apparatus, appliance, software, material or other article, whether used alone or in combination, including the software intended by its manufacturer to be used specifically for diagnostic and/or therapeutic purposes and necessary for its proper application, intended by the manufacturer to be used for human beings. Devices are to be used for the purpose of: 10 • Diagnosis, prevention, monitoring, treatment or alleviation of disease.
Diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap.
Investigation, replacement or modification of the anatomy or of a 15 physiological process
• Control of conception
This includes devices that do not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means.
In more detail formulations (synonymous applications or compositions) can mean for example antimicrobial cleansers, soaps, anti-fouling and antimicrobial paints for inside and outside use, antimicrobial wallpapers, antimicrobial dressings and plasters, prostheses and bone cement with antimicrobial activity, dental fillings, dental prostheses, formulations against gastrointestinal infections, active coal, antimicrobial cat litter, antimicrobial diapers, tampons or sanitary towels, ambient fragrances for rooms or cars, formulations for oral or body care, absorbent pads, air conditioning (filters and ducts), air inflated construction (air halls), agricultural and mulch films,
O U all purpose adhesives, appliances and equipment, appliance adhesives and sealants, aprons, artificial leather, artificial plants, artificial wood, piastic lumber, astroturf, automobile parts, automotive and truck upholstery, awnings, bags, bandages, barrier fabrics, bathroom accessories, bathtubs, bedding, beverage dispensers, bibs, boats, boat covers, book covers, bottles, brush bristles, brush handles, brooms, building components (walls, wallboard, floors, concrete, siding, roofing, shingles, hardware, carpet cleaner, ceilings and commercial and industrial applications), cable sheathing, caps (hats), cardboard, carpet and carpet underlay, caster wheels, cat litter, clinical thermometers, coats, compact discs, convertible tops, cookware, coolers, cooling towers, counter and table tops, conveyor belts, countertops, credit cards, crates (food and non-food), cups, currency, curtains, cushion pads, cutting boards, decking, dishes, dish cloths, dishwasher components, diving equipment or snorkels, drainage sewer pipe, draperies, exercise equipment, equipment for slaughterhouses or creameries or diaries, equipment for gyms, saunas or massages, fan blades, fibrefill, filters, fittings, fences, floor coverings, floor and carpet baking, flooring, foam (cushion, mattress), food preparation appliances, food and beverage processing equipment, food and drink containers, storage and bags, food handling equipment, food packaging, food and meat crates, food trays and covers, food wrap, footwear (including boots, sports equipment, and tools), fruit and vegetable brushes, fruit crates, furniture, garbage bags, garbage cans, garment bags, gaskets, general purpose containers, gloves, gowns (medical and consumers), grease traps, rigid greenhouses, greenhouse films, grout and joint compound, heating, ventilation and air conditioning, hoses, ice-making equipment and trays, incontinence care products, indoor and outdoor furniture, industrial equipment, inflatable bed, insulation for wire and cable, insulators, intimate apparel, jacket liners, janitorial equipment, kitchen and bathroom hardware, kitchen sinks and fixtures, kitchen towels, laminate and tile adhesives, laying batteries, life vests, liners, mats, mattress cover pads and filing, mattress adhesives, medical and dental apparel, mobile homes, mobile toilets, mops, money, natural and synthetic fibres and fabrics, non-woven fabrics, outerwear, packaging, pallets, paper products (wipes, tissues, wall coverings, towels, book covers, mulch), pillow covers, pipes, pipe sealant and insulating materials, plaster, plastic films, plates and utensils, playground equipment, plumbing supplies and fixtures (including toilet bowl seats), plumbing adhesives and sealants, pool liners, process vessels, protective covers, refrigerator components, roofing sheets, membranes, shingles and flashing, ropes, rugs, sales counter, sails, sanitary pipes, sealing compounds for bathrooms, kitchens or glass, sheets and blankets, shoes, shoe insoles, shower curtains, shower tubs, siding for housing, silage wrap , silos, sinks, siphons, skylights, sleeping bags, sleepwear, socks and hosiery, sponges, sprinkler, sportswear and sports equipment, storage containers, stucco, sun roof, sun shades, napkins, tanks, tape, tarps, telephone boxes or public phones, tents and other outdoor equipment, ticking (mattress pillow), tiles, tile grout, toothbrush handle and bristles, toilet paper and handkerchiefs, toilet blocks and cleaners, towels, toothbrush tumbler, toys, trim for outerwear and garments, trunk liners, tubing, umbrellas, undergarments, uniforms, upholstery, vacuum cleaner bags, wall and floor covering, wallpaper, waste bags, water tanks, waste containers, water treatment, water and ice handling equipment and filters, wet suits, wipes, wire and cable, wood, wood filled plastics.
The compositions according to the invention may include or comprise, essentially consist of or consist of the said necessary or optional constituents. All compounds or components which can be used in the agents or compositions are either known and commercially available or can be synthesised by known processes.
The invention likewise relates to a process for the preparation of a composition as described above, characterised in that at least one compound of formula I as described above is mixed with a carrier and optionally with further active compounds or auxiliaries. The carriers and optionally the further active compounds or auxiliaries depends on the application field of the inventive composition and are known to the skilled artisan in said field of application.
Preferably the composition comprising at least one compound of formula I according to the present invention is a cosmetic formulation. Cosmetic formulations can be in the form of solutions, suspensions, emulsions, pastes, ointments, gels, creams, lotions, powders, oils, waxes, pencils, shampoos, deodorants-creames, gels, lotions, emulsions, deodorant sticks, roll-ons, aerosols, sprays, pump sprays or lacquers, especially nail lacquers. In all these applications the antimicrobial activity of the compositions according to the present invention can advantageously be used. In particular in the case of water-based inks, paints and preparations, the antimicrobial activity is of great importance due to rapid fouling and contamination with bacteria of materials in these application areas. The amount of at least one compound of formula I is not crucial per se and can be adapted in each case to obtain the most effective result. Depending on the formulation or application the content preferably lies in the range of 0.005% to 100% per weight, based on the composition in total. (100% if used as pure ionic liquid for cleaining surface areas etc.). For cosmetic formulations the content preferably lies in the range of 0.005% to 2% per weight, preferably in the range of 0.01 to 1% per weight, particularly preferably in the range of 0.02% to 0.5% per weight, based on the composition in total.
In all above-mentioned applications the compositions according to the present invention can advantageously be combined with all known preservatives or antimicrobial agents, such as for example phenoxyethanol, triclosan, 7-ethylbicyclooxazolidine, benzoic acid, bronopol, butylparaben, chlorphenesin, diazolidinyl urea, dichlorobenzyl alcohol, dimethyl oxazolidine, DMDM hydantoin, ethylparaben, hexamidine diisethionate, imidiazolidinyl urea, imidiazolidinyl urea NF, iodopropynyl butylcarbamate, isobutylparaben, methylparaben, potassium sorbate NF FCC, propylparaben, quaternium-15, sodium benzoate NF FCC, sodium caprylate, sodium dehydroacetate, sodium dehydroacetate FCC1 sodium hydroxymethylglycinate, sodium methylparaben, sodium propylparaben, sorbic acid NF FCC, anisic acid, benzethonium chloride, caprylic/capric glycerides, caprylyl glycol, di-alpha-tocopherol, ethylhexylglycerin, glyceryl caprate, methyl isothiazolinone, polymethoxy bicyclic oxazolidine. tocopheryl acetate, benzalkonium chloride, camellia sinensis leaf extract, Candida bombicola/glucose/methyl rapeseedate, hydrogen peroxide, methylbenzethonium chloride phenol, pinus pinaster bark extract,
Poloxamer 188, PVP-lodine, Rosmarinus officinalis Leaf extract, Vitis vinifera seed extract, ammomium benzoate, ammonium propionate, 5- bromo-5-nitro-1 ,3-dioxane, chloroxylenol, ethyl alcohol, glutaral, iodopropynyl butylcarabamate, isothiazolinone, parabens, pircotone olamine, selenium disulphine, sorbic acid, zinc pyrithione, dehydroacetic acid, dimethyl hydroxmethyl pyrazole, formaldehyde, hexetidine, methyldibromo glutaronitrile, salicylic acid, sodium iodate, zinc oxide, benzyl alcohol, boric acid, chloroacetamide, phenoxythanol, ortholphenylphenol, 7-ethyl bicycloxazolidine, imidazolidinyl urea, methenammonium chloride, methylbromo glutaronitrile, polymethoxy bicylooxazolidine, Thimersal, chlorhexidine, phenethyl alcohol, polyaminopropyl biguanide, polyquartemium-42, Triclocarban, zinc phenolsulphonate, chlorobutanol, Neem seed oil, Tee trea oil, Usnic acid, ammonium benzoate, benziosthiazolinone, benzotriazole, benzylhemiformal, 2-bromo-2-notropropane-1 ,3-diol, butyl benzoate, calcium benzoate, calcium paraben, calcium propionate, calcium salicylate, calcium sorbate, captan, Chloramine T, chlorhexidine diacetate, chlorhexidine digluconate, chlorhexidine dithydrochloride, chloroacetamine, p-chloro-m-cresol, chlorophene, p-chlorophenol, chlorothymol, Citrus Grandis (Grapefruit) Fruit Extract, Citrus Grandis (Grapefruit) Seed Extract, Copper Usnate, m-cresol, o-cresol, p-cresol, DEDM Hydantoin, DEDM Hydantoin Dilaurate, Dibromopropamidine Diisethionate, Dimethyl Hydroxy methyl Pyrazole, Dimethylol Ethylene Thiourea, dithiomethylbenzamide, DMHF, Domiphen Bromide, Ethyl Ferulate, Ferulic Acid, Glycerol Formal, Glyoxal, Hexamidine, Hexamidine Diparaben, Hexamidine Paraben, 4-Hydroxybenzoic Acid, Hydroxymethyl Dioxazabicyclooctane, Isodecylparaben, lsopropyl Cresols,
Isopropylparaben, lsopropyl Sorbate, Magnesium Benzoate, Magnesium Propionate, Magnesium Salicylate, MDM Hydantoin, MEA-Benzoate, MEA o-Phenylphenate, MEA-Salicylate, Methylchloroisthiazolinone, Methylisothazolinone, Mixed Cresols, Nisin, PEG-5 DEDM Hydantoin, PEG-15 DEDM Hydantoin, PEG-5 Hydantoin Oleate, PEG-15 DEDM
Hydantoin Stearate, Phenol, , Phenoxyethylparaben, Phenoxyisopropanol, Phenyl Benzoate, Phenyl Mercuric Acetate, Phenyl Mercuric Benzoate, Phenyl Mercuric Borate, Phenyl Mercuric Bromide, Phenyl Mercuric Chloride, Phenylparaben, o-Phenylphenol, Polyaminopropyl Biguanide Stearate, Polyquaternium-42; Potassium Benzoate, Potassium
Ethylparaben, Potassium Methylparaben, Potassium Paraben, Potassium Phenoxide, Potassium o-Phenylphenate, Potassium Propionate, Potassium Propylparaben, Potassium Salicylate, Potassium Sorbate, Propionic Acid, Propyl Benzoate, Quatemium-8, Quatemium-14, Silver Borosilicate, Silver Magnesium Aluminium Phosphate, Sodium Benzoate, Sodium
Butylparaben, Sodium p-Chloro-m-Cresol, Sodium Ethylparaben, Sodium Formate, Sodium Hydroxymethane Sulfonate, Sodium Isobutylparaben, Sodium Paraben, Sodium Phenolsulfonate, Sodium Phenoxide, Sodium o- Phenylphenate, Sodium Propionate, Sodium Pyrithione, Sodium Salicylate, Sodium Sorbate, TEA-Sorbate, Thimerosal, Undecylenoyl PEG-5 Paraben, Zinc Pyrithione or combinations thereof, such as for example Benzyl alcohol/mehtylchloroisothiazolinone/methylisothiazolinone, Benzyl alcohol/PPG-2 methyl ether/bronopol/deceth- 8/iodopropynyl/butylcarbamate, Chloroacetamide sodium benzoate, Dehydroacetic acid/benzyl alcohol, Diazolidinyl urea/iodopropynyl butylcarbamate, Diazolidinyl urea/methylparaben/ethylparaben/butylparaben/propylparaben/isobutylpara ben/2-phenoxyethanol, DMDM hydantoin/iodopropynyl butylcarbamate, Glycerin/water/ethoxdiglycol/caprylyl glycol/sodium polyacrylate, Glyceryl laurate/caprylyl/phenylpropanol/dipropylene glycol, Isopropylparaben/isobutylparaben/butylparaben, Methyl chloroisothiazolinone/methyl isothiazolinone, Methyldibromo glutaronitrile/methylchloroisothiazolinone/methylisothiazolinone/phenoxyeth anol, Methyldibromo glutaronitrile/phenoxyethanol, Methylchloroisothiazolinone/methylisothiazolinone, Methylparaben/ethylparaben/butylparaben/propylparaben/butylenes glycol, Methylparaben/ethylparaben/butylparaben/propylparaben/isobutylparaben, Methylparaben/ethylparaben/butylparaben/propylparaben/isobutylparaben/ 2-phenoxy-ethanol/bronopol,
Methylparaben/ethylparaben/butylparaben/propylparaben/1 ,3-butylene glycol isomer, Methylparaben/propylparaben, Methylparaben/propylparaben/benzyl alcohol,
Methylparaben/propylparaben/bronopol/phenoxyethanol, Methylparaben/propylparaben/bronopol/propylene glycol, Methylparaben/propylparaben/ethylparaben, Methylparaben/propylparaben/propylene glycol/diazolidinyl urea, Phenoxyethanol/benzoic acid/dehydroacetic acid, Phenoxyethanol/benzyl alcohol/potassium sorbate/tocopherol,
Phenoxylethanol/chlorphenesin/glycerin/methylparaben/benzoic acid, Phenoxyethanol/DMDMhydantoin/lodopropynyl butyl carbamate, Phenoxyethanol/DMDM hydantoin/methylparaben/propylparaben, Phenoxyethanol/isopropylparaben/isobutylparaben/butylparaben,
Phenoxyethanol/methyldibromo glutaronitrile/idopropynyl butylcarbamate, Phenoxyethanol/methylparaben/butylparaben/ethylparaben/propylparaben, Phenoxyethanol/methylparaben/butylparaben/ethylparaben/propylparaben/i sobutyl-paraben, Phenoxyethanol/methylparaben/isobutylparaben/butylparaben,
Phenoxythanol/triethylene glycol/dichlorobenzyl alcohol, Polyaminopropyl biguanide/parabens/phenoxyethanol, PPG-2 methyl ether/sodium benzoate/potassium sorbate/iodopropynyl butylcarbamate, Propylene glycol/benzyl alcohol/methylchloroisothiazolinone/methylisothaizolinone, Propylene glycol/diazolidinyl urea/iodopropynyl butylcarbamate, Propylene glycol/diazolidinyl urea/methylparaben/propylparaben, Propylene glycol/MDMD hydantoin/methylparaben, Propylene glycol/MDMD hydantoin/methylparaben/propylparaben, Propylene glycol/lichen extract, Propylene glycol/phenoxyethanol/chlorphenesin/methylparaben, Sodium levulinate/phenylpropanol combinations. The combination of compounds of formula I according to the present invention with preservatives or antimicrobial agents shown above may help to boost the antimicrobial performance of the preservative or antimicrobial agent in a formulation. This may even allow to decrease the amount of the preservative or antimicrobial agent in formulations or applications, thus avoiding or decreasing undesired effects that are associated with the use of said preservative or antimicrobial agent such as adverse effects to skin, hair or the environment.
Furthermore, compounds of formula I in compositions according to the present invention can be advantageously combined with other antibiotics. Antibiotics in this sense mean all known antibiotics, for example selected from the group of Beta-lactam, Vancomycin, Macrolides, Tetracyclines, Quinolones, Fluoroquinolones, Nitrated compounds (as for instance Nitroxoline, Tilboquinol or Nitrofurantoin), Aminoglycosides, Phenicols, Lincosamids, Synergistins, Fosfomycin, Fusidic acid, oxazolidinones, Rifamycins, Polymixynes, Gramicidins, Tyrocydine, Glycopeptides, Sulfonamides or Trimethoprims. Combinations of compositions and antibiotics are advantageous with respect to the resistance of several microorganisms against certain antibiotics. A combination of antibiotics with compositions according to the present invention helps to overcome the resistance by simply decreasing the number of microorganisms, which have not been affected by the antibiotics. In several application areas the antimicrobial activity can be useful in several stages of the processing. For example plastics or polymers comprising compounds of formula I according to the present invention can be stored in the form of Masterbatches for a long period of time, without risking the contamination of the Masterbatch with microorganisms. The
Masterbatch can be processed in the same way as all known Masterbatches. The therewith-obtained products are useful in building and construction, household, items and furnishing, electrical and electronics parts, apparel, textiles and fabrics, coatings and laminates, transportation and recreation, adhesives, sealants and grouts, food contact items and water contact items, such as for example plastic bottles, bottle caps, films, coextrusion films, exterior and interior automotive parts etc, having surfaces, which again show antimicrobial activity. In particular bottles and films comprising compositions according to the present invention are of interest with respect to the decrease of the number of microorganisms in therein-packaged products and consumer goods. Also plastics or polymers used in baths, swimming pools, kitchens, joints compounds, sealing compounds or in other generally humid surroundings can advantageously be provided with compositions according to the present invention. Suitable plastics and polymers from which the articles are fabricated include synthetic, natural and semisynthetic organic polymers. Example of polymers that can be used to practice this invention include, but are not limited to, aliphatic and aromatic polyesters, including polyethylene terephthalate, polybutylene terephthalate, polyethylene isophthalate, polyhexamethylene terephthalate, polylactic acid, polyglycolic acid, and liquid crystalline polymers for high performance resins and fibers; polyester block copolymers; aliphatic and aromatic polyamides including nylon 6, nylon 66, nylon 610, nylon 11 , nylon 12, nylon 1212, poly-p-phenylene terephthalamide, poly-m-phenylene isophthalamide; copolymerised polyamides; polyolefins including polyethylene, polypropylene, and copolymers thereof; vinyl polymers, including polystyrene, polyacrylonitrile, polyvinylalcohol, polyvinyl acetate, polyvinylchloride, polyvinylidene chloride, ABS resins and acrylic resins; copolymers of ethylene and vinyl acetate; fluorocarbon polymers, including polytetrafluoroethylene. polyvinylidene fluoride and polyvinyl fluoride; polyurethanes; segmented polyurethane elastomers, spandex or elastane elastomers; polyethers, including polyacetals; polyketones, polyetherether ketone (PEEK), polyether ketoneketone (PEKK); polyether and polyester block polymers; polysulfides; polysulfones: polysiloxanes such as polydimethyl siloxane; polycarbonates; thermosetting synthetic polymers such as phenol-formaldehyde copolymer, polyurethane, polyesterurethane, polyetherurethane, polyetherurethaneurea, polyesterurethaneurea; natural polymers such as cellulosics, cotton and wool; and regenerated or semi-synthetic polymers such as rayon, cuprammonium rayon, acetate rayon, triacetate rayon, reconstituted silk and polysaccharides. This group includes reasonable copolymers, terpolymers and blends of many of the species listed. Spandex is defined herein to refer to a fiber or filament made from a long chain synthetic polymer that comprises at least 85 % by weight of segmented polyurethane.
The polymer articles of this invention can be, for example, in the shape of films, fibers, powders, granules or articles made there from such as containers, pipes and monofilaments for brushes. When a high degree of antimicrobial effect is desired, the molded article preferably has a large surface area.
A polymer article of the present invention having antimicrobial properties is comprised of at least one compound of formula I and at least one organic polymer.
The polymer articles according to the present invention may contain other additives as well. They may contain, for example, polymerization catalysts, stabilizers, delustering agents, optical whitening agents, organic or inorganic pigments, inorganic fillers, plasticizers and so on. Examples of plastics which can be used here as well as preparation and processing methods can be found in RD 472005 or R. Glausch, M. Kieser, R. Maisch, G. Pfaff, J. Weitzel, Perlglanzpigmente, Curt R. Vincentz Verlag, 1996, 83 ff.
Paints and lacquers comprising compounds of formula I according to the present invention can be waterborne or solvent-based. They can be on the basis of synthetic or chemically modified natural polymers, such as for example, acryl polymers, vinyl polymers, alkyd resins, phenol resins, urea resins, melamine resins, polyester resins, cellulose nitrate, epoxy resins polyurethane resins, bitumen, tar, shellac, natural rubber or resins, and can comprise all known additives and adjuvants, such as for example sikkatives, waxes, dispersing agents, anti-blocking agents or drying agents. Paints and lacquers provided with compositions can be used for example in the automotive area or in the industrial area, in powder coatings, architectural use, as coating of wood, steel, inner walls, floors, blankets, facades or in humid surroundings thus providing the surfaces antimicrobial activity. Furthermore the coating is stabilized against attacks of microorganisms thus enhancing the durability of the coatings.
Compounds of formula I or compositions comprising compounds of formula I according to the present invention can advantageously be applied to all kinds of printing inks, such as liquid inks, UV curable inks, paste inks and paper coatings. Known preparations for these appliation areas lack sufficient stability against antimicrobial contamination, especially in water based systems. The usage of compounds or compositions according to the present invention can help to minimize the contamination with microorganisms thus allowing to decrease the necessary content of preservatives. The therewith provided preparations are stable for a long period of time. The liquid inks can be water based, based on water/alcohol mixtures or solvent based. Suitable binders for aqueous inks are acrylates, methacrylates, polyesters and polyurethanes. Binders for solvent based inks are nitrocellulose, ethylcellulose, polyamide, PVC/PVA-copolymers, polyvinylbutyrale, clorinated rubber, rosin modified phenolic resins, maleinic resins, calcium/zinc-resinate-EHEC, acrylates and mixtures thereof. Solvents which can be used in solvent based inks are ethanol, isopropanol, n-propanol, aceton, ethylacetate, isopropylacetate, n-propylacetate, methoxypropanol, ethoxypropanol, toluene, aliphatic hydrocarbons and mixtures. UV-curable printing inks are basically composed of a binder and a liquid monomer, such as epoxy acrylates, polyurethane acrylates, polyester acrylates as reactive monomers hexanediol diacrylate, di/tripropyleneglycol diacrylate, trimethylpropane triacrylate, trimethylolpropaneethoxy triacrylate and mixtures thereof.
Paste inks containing compounds according to the present invention can further contain rosin modified phenolic resins, maleinic acid modified resins, alkyd resins, linseed/soibean oil based resins, hydrocarbon based resins and mineral oils, linseed oil or soybean oil as solvents. Paper coatings containing antimicrobial compounds may further contain starch, protein/casein, polyvinyl alcohol, latexes, carboxymethyl cellulose or acrylate binders.The printing inks may further contain known fillers and rheology modifiers. More information on technology and compositions of printing inks is provided by R. L. Leach, R. J. Pierce, in The Printing Ink Manual, Fifth Edition, Blueprint, London, 1993.
Furthermore, deodorants may be a special form of cosmetic formulations according to the present invention. Different forms of deodorants are in mind: deodorant-cremes, gels, lotions, emulsions, deodorant sticks, RoII- ons, sprays and pump sprays. The compounds of formula I are combined with a suitable carrier material used in deodorants. Examples of suitable carrier materials are glyceryl stearate, aluminium chlorohydrate, propylene glycol, carbomer, glycerin, dicapryl ether, ethanol, glyceryl cocoate, cylomethicone, dimethicone, dipropylene glycol, stearyl alcohol, mineral oil, phenyltrimethicone or sodium stearate. The odour production of the skin is the result from the modifications of initially odourless secretions from the apocrine glands, such as for example lipids, proteins, ammonia, steroids and reducing sugars, by microorganisms, like for example Staphylococcus, Corynebacterium or malassezia. The inventive compounds of formula I are effective against the Gram-positive cocci group, for example against the Micrococcaceae family (Staphylococcus aureus, staphylococcus epidermidis, staphylococcus hominis), against the Gram-positive rods, for example against the Coryneforms family (Brevibacterium and /or corynebacterium for example) causing malodour of the skin, which can be reduced by deodorants comprising these compounds of formula I. The deodorants may comprise various adjuvants used in this type of composition, such as scents or perfumes, other preservatives, electrolytes, silicone derivatives, dyes and/or pigments which colour the composition itself, or other ingredients customarily used for deodorants. Further ingredients that can be incorporated into the formulations are described later in this application in more detail.
Compositions according to the present invention can also be used for oral care, for example for prophylaxis and/or treatment of dental plaque, caries or oral malodour. oral malodour, caries and dental plaque are caused by microorganisms, for example by Streptococcus sobrinus, Streptococcus mutans, Streptococcus gordonii, Streptococcus salivaris, Streptococcus sanguis, Actinomyces, Lactobacilli, Fusobacterium, Veillonella, Treponema, denticola, Porphyromonas. gingivalis, Bacteroides or Peptostreptococcus.
The oral composition may be formulated for use in any form of interdental or periodontal treatment and may be in the form, for example, of a dentifrice, mouthwash, toothpowder, chewing gum, lozenge, mouth spray, floss, dental paint, or glass ionomer cement. Use of the antimicrobial material of the present invention in a glass ionomer cement has the advantage of providing X-ray opacity as well as antimicrobial action. Such compositions may, as appropriate, contain conventional materials such as, for example, humectants, surfactants, gelling agents, abrasives or low abrasive spheres, fluoride sources, desensitizing agents, flavorings, colorings, sweeteners, preservatives, structuring agents, bactericides, anti- tartar agents and anti-plaque agents.
Suitable humectants for use in dentifrice compositions include polyhydric alcohols such as xylitol, sorbitol, glycerol, propylene glycol and polyethylene glycols. Mixtures of glycerol and sorbitol are particularly effective. A humectant helps to prevent dentifrice compositions from hardening on exposure to air, and may also provide a moist feel, smooth texture, flowability, and a desirable sweetness in the mouth. Suitably, such humectants may comprise from about 0% - 85 %, preferably from about 0% - 60 % by weight of the oral hygiene composition.
Compositions comprising at least one compound of formula I according to the present invention usually comprise several ingredients. In the following examples of commonly used ingredients, especially for cosmetic formulations, are given.
Preferred formulations or applications additionally comprise at least one insect repellent, preferably selected from the group ethyl 3-(N-n-butyl-N- acetylamino)propionate, 2-(2-hydroxyethyl)-1 -methylpropyl 1 -piperidine- carboxylate, N,N-diethyl-3-methylbenzamide, dimethyl phthalate, butopyro- noxyl, 2,3,4,5-bis(2-butylene)tetrahydro-2-furaldehyde, N,N-diethylcapryl- amide, N,N-diethylbenzamide, o-chloro-N.N-diethylbenzamide, dimethyl carbate, di-n-propyl isocinchomeronate, 2-ethylhexane-1 ,3-diol, N-octylbi- cycloheptenedicarboximide or piperonyl butoxide, particularly preferably selected from the group 3-(N-n-butyl-N-acetylamino)propionate, 2-(2- hydroxyethyl)-1 -methylpropyl 1-piperidinecarboxylate or N,N-diethyl-3- methylbenzamide. These insect repellents are generally incorporated into cosmetic formulations in an amount of from 0.5% to 20% by weight, preferably 1 % - 8% by weight, based on the composition in total.
Preferred formulations or applications additionally comprise at least one UV filter resulting in antimicrobial preparations having light protection properties. The UV filter can preferably be selected from the group of dibenzoylmethane derivatives. The dibenzoylmethane derivatives used within the scope of the present invention are products which are already well known per se and are described, in particular, in the specifications FR- A-2 326 405, FR-A-2 440 933 and EP-A-O 114 607.
In principle, all known UV filters are suitable for combination with dibenzoylmethane derivatives and with the compounds of the formula I according to the invention, for example one or more additional hydrophilic or lipophilic sun-protection filters which are effective in the UV-A region and/or UV-B region and/or IR and/or VIS region (absorbers). These additional filters can be selected, in particular, from cinnamic acid derivatives, salicylic acid derivatives, camphor derivatives, triazine derivatives, β,β-diphenyl acrylate derivatives, p-aminobenzoic acid derivatives and polymeric filters and silicone filters, which are described in the application WO 93/04665. Further examples of organic filters are indicated in Patent Application EP-A 0 487 404. Particular preference is given to UV filters whose physiological acceptability has already been demonstrated. Both for UVA and UVB filters, there are many proven substances which are known from the specialist literature.
These organic UV filters are generally incorporated into cosmetic formulations in an amount of from 0.5% to 10% by weight, preferably 1% - 8% by weight, based on the composition in total. It may furthermore be preferred in accordance with the invention for the preparations to comprise further inorganic UV filters. Preference is given here both to those from the group consisting of titanium dioxides, such as, for example, coated titanium dioxide (for example Eusolex® T-2000 or Eusolex®T-AQUA), zinc oxides (for example Sachtotec®), iron oxides and also cerium oxides. These inorganic UV filters are generally incorporated into cosmetic preparations in an amount of from 0.5% to 20% by weight, preferably 2% - 10% by weight, based on the compositin in total. In particular, it may be preferred here for a UV-Filter to be incorporated into one phase of emulsions and a further inorganic UV filter to be incorporated into the other phase.
Furthermore it is preferred to combine compounds of formula I according to the present invention with antioxidants, humectants, vitamins such as panthenol, or vitamin B6 derivatives (e.g. niacin amide) or any derivative of ascorbic acid, skin and hair care actives, in particular watersoluble actives such as carnitine, creatinine, creatine, ectoin, dihydroxyacetone, quaternized actives, and bioflavanoids such as troxerutin or isoquercetin_or
UV filters like phenyl benzimidazole sulfonic acid
Preferred auxiliaries originate from the group consisting of stabilisers, solubilisers, colorants and odour improvers.
Ointments, pastes, creams and gels may comprise the customary excipi- ents, for example animal and vegetable fats, waxes, paraffins, starch, tra- gacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc and zinc oxide, or mixtures of these substances.
Powders and sprays may comprise the customary excipients, for example lactose, talc, silica, aluminium hydroxide, calcium silicate and polyamide powder, or mixtures of these substances. Sprays may additionally comprise the customary propellants, for example chlorofluorocarbons, propane/butane or dimethyl ether.
Solutions and emulsions may comprise the customary excipients, such as solvents, solubilisers and emulsifiers, for example water, ethanol, isopro- panol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butyl glycol, oils, in particular cottonseed oil, peanut oil, wheatgerm oil, olive oil, castor oil and sesame oil, glycerol fatty acid esters, polyethylene glycols and fatty acid esters of sorbitan, or mixtures of these substances.
Suspensions may comprise the customary excipients, such as liquid dilu- ents, for example water, ethanol or propylene glycol, suspending agents, for example ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminium metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances.
Soaps may comprise the customary excipients, such as alkali metal salts of fatty acids, salts of fatty acid monoesters, fatty acid protein hydrolysates, isethionates, lanolin, fatty alcohol, vegetable oils, plant extracts, glycerol, sugars, or mixtures of these substances.
Surfactant-containing cleansing products can comprise the conventional carriers, such as salts of fatty alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic acid monoesters, fatty acid albumen hydrolysates, isothionates, imidazolinium derivatives, methyl taurates, sarcosinates, fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable and synthetic oils, lanolin derivatives, ethoxylated glycerol fatty acid esters or mixtures of these substances.
Face and body oils may comprise the customary excipients, such as synthetic oils, such as fatty acid esters, fatty alcohols, silicone oils, natural oils, such as vegetable oils and oily plant extracts, paraffin oils or lanolin oils, or mixtures of these substances.
Further typical cosmetic application forms are also shampoos, lipsticks, lip- care sticks, mascara, eyeliner, eye-shadow, rouge, powder make-up, emulsion make-up and wax make-up, and sunscreen, pre-sun and after- sun preparations.
The preferred preparation forms according to the invention include, in particular, emulsions.
The aqueous phase of the preparations according to the invention optionally advantageously comprises alcohols, diols or polyols having a low carbon number, and ethers thereof, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene glycol monomethyl or monoethyl ether and analogous products, furthermore alcohols having a low carbon number, for example ethanol, isopropanol, 1 ,2-propanediol or glycerol, and, in particular, one or more thickeners, which may advantageously be selected from the group consisting of silicon dioxide, aluminium silicates, polysaccharides and deriva- tives thereof, for example hyaluronic acid, xanthan gum, hydroxypropyl- methylcellulose, particularly advantageously from the group consisting of the polyacrylates, preferably a polyacrylate from the group consisting of the so-called Carbopols, for example Carbopol grades 980, 981 , 1382, 2984 or 5984, in each case individually or in combination.
Cosmetic and dermatological preparations according to the invention may exist in various forms. Thus, they may be, for example, a solution, a water- free preparation, an emulsion or microemulsion of the water-in-oil (W/O) or oil-in-water (O/W) type, a multiple emulsion, for example of the water-in-oil- in-water (W/O/W) type, a gel, a solid stick, an ointment or an aerosol. It is also advantageous to administer ectoins in encapsulated form, for example in collagen matrices and other conventional encapsulation materials, for example as cellulose encapsulations, in gelatine, wax matrices or liposo- mally encapsulated. In particular, wax matrices, as described in DE-A
43 08 282, have proven favourable. Preference is given to emulsions. O/W emulsions are particularly preferred. Emulsions, W/O emulsions and O/W emulsions are obtainable in a conventional manner.
Emulsifiers that can be used are, for example, the known W/O and O/W emulsifiers. It is advantageous to use further conventional co-emulsifiers in the preferred O/W emulsions according to the invention. The commercially available product Ceralution C (Sasol) has to be proven to be in particular advantageous as emulsifier.
Co-emulsifiers which are advantageous according to the invention are, for example, O/W emulsifiers, principally from the group consisting of the substances having HLB values of 11-16, very particularly advantageously having HLB values of 14.5-15.5, so long as the O/W emulsifiers have satu- rated radicals R and R'. If the O/W emulsifiers have unsaturated radicals R and/or R' or in the case of isoalkyl derivatives, the preferred HLB value of such emulsifiers may also be lower or higher. The preparation may comprise cosmetic adjuvants which are usually used in this type of preparation, such as, for example, thickeners, softeners, moisturisers, surface-active agents, emulsifiers, preservatives, antifoams, perfumes, waxes, lanolin, propellants, dyes and/or pigments which colour the composition itself or the skin, and other ingredients usually used in cosmetics.
Emulsions according to the invention are advantageous and comprise, for example, the said fats, oils, waxes and other fatty substances, as well as water and an emulsifier, as usually used for a preparation of this type.
The lipid phase may advantageously be selected from the following group of substances:
- mineral oils, mineral waxes;
- oils, such as triglycerides of capric or caprylic acid, furthermore natural oils, such as, for example, castor oil;
- fats, waxes and other natural and synthetic fatty substances, preferably esters of fatty acids with alcohols having a low carbon number, for example with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with alkanoic acids having a low carbon number or with fatty acids;
- silicone oils, such as dimethyipolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms thereof.
For the purposes of the present invention, the oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions is advantageously selected from the group consisting of esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 3 to 30 carbon atoms and saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of from 3 to 30 carbon atoms, or from the group consisting of esters of aromatic carboxylic acids and saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of from 3 to 30 carbon atoms. Ester oils of this type can then advantageously be selected from the group consisting of isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, 2-octyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyl oleate, erucyl erucate and synthetic, semi-synthetic and natural mixtures of esters of this type, for example jojoba oil.
The oil phase may furthermore advantageously be selected from the group consisting of branched and unbranched hydrocarbons and waxes, silicone oils, dialkyl ethers, or the group consisting of saturated and unsaturated, branched and unbranched alcohols, and fatty acid triglycerides, specifically the triglycerol esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 8 to 24, in particular 12-18, carbon atoms. The fatty acid triglycerides may advantageously be selected, for example, from the group consisting of synthetic, semi-synthetic and natural oils, for example olive oil, sunflower oil, soya oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil and the like.
Any desired mixtures of oil and wax components of this type may also advantageously be employed for the purposes of the present invention. It may also be advantageous to employ waxes, for example cetyl palmitate, as the only lipid component of the oil phase.
In comparison to the unique properties of compounds of formula I with regard to the broad applicability to various bacteria, fungi and yeasts, related compounds are specially designed as being inhibitors for the growth of staphylococcus epidermidis and pseudomonas aeruginosa.
Theses related compounds are
N-ethyl-N,N-dimethyl-2-methoxyethylammonium acetate, N-ethyl-N,N- dimethyl-2-hydroxyethylammonium acetate and N-ethyl-N,N-dimethyl-2- hydroxyethylammonium propionate. They are effective against special bacteria e.g. staphylococcus epidermidis and pseudomonas aeruginosa.
These compounds will be useful as antibiotics in the broad sense as described above.
The invention therefore relates likewise to the use of said compounds as antibiotics and to the substances
N-ethyl-N,N-dimethyl-2-methoxyethylammonium acetate and N-ethyl-N,N- dimethyl-2-hydroxyethylarnmoniurn propionate itself.
In addition, these three related compounds as stated above falls in the definition of being an ionic liquid. Therefore these three related compounds may be used as solvent or solvent additive, as phase-transfer catalyst, as extractant, as heat-transfer medium, as surface-active substance, as plasticiser, as flame retardant, as conductive salt or additive in electrochemical cells as described above.
Further fields of applications of these three related compounds are solvents for carbohydrate containing solids in particular biopolymers and derivatives or degredation products thereof. In addition, these compounds can be applied as lubricants, working fluids for maschines, such as compressors, pumps or hydraulic devices. These ionic liquids according to this invention may be also used in electro-chemical cells in particular for electo-optical cells or as functional materials in sensors.
The most preferred use of these three ionic liquids is the use as antibiotic against, preferably as antibiotic against staphylococcus epidermidis and pseudomonas aeruginosa..
The invention likewise relates to a process for the production of N-ethyl-
N,N-dimethyl-2-methoxyethylammonium acetate and N-ethyl-N,N-dimethyl- 2-hydroxyethylammonium propionate in which the corresponding ammonium halogenides in which the halide is Cl", Br" or I", are converted to Hydroxides via ion exchange followed by reaction with acetic acid or propionic acid. The same details to the process applies as mentioned above for the syntesis of compounds of formula I.
The entire disclosure of all applications, patents and publications, cited above are hereby incorporated by reference.
The compounds and their production process as well as compositions according to the present invention is more illustratively demonstrated but not limited by means of the following examples.
Examples:
Example 1. Synthesis of N-ethyl-N,N-dimethyl-2- hydroxyethylammonium acetate (1130)
(CAS 21618-33-7)
A. Alkylation
Br
A solution of 1 L 2-(dimethylamino)-ethanol dissolved in 2,5 L acetonitrile is mixed by mechanical stirring and heated to 80 0C. To this solution, 0,82 L bromoethane is added slowly and stirred for a period of 30 minutes at this temperature.
After 2 h the reaction mixture is added to ethylacetate and the ammonium bromide is precipitated. After separation of the product and washing with ethyl acetate, 1897 g is obtained as white solid.
B. Anion Exchange
0.72 kg anion exchanger III is washed with water in a type G3 glass filter and dried. Afterwards, a solution of 120 g N-ethyl, N,N-dimethyl-2-hydroxy- ethylammonium bromide in 500 ml water is added. The pH of the solution after ion exchange is about pH 14. The content of bromide is about 51 mg/L.
C. Neutralisation with Acetic Acid
While stirring, 8 ml_ acetic acid is added to 225 ml aqueous solution ot N- ethyl-N,N-dimethyl-2-hydroxyethylammoniurn hydroxide at room temperature. After distillation of the solvent, 26 g N-ethyl-N,N-dimethyl-2- hydroxyethylammonium acetate is obtained as clear liquid.
1 H NMR (d6-DMSO): δ = 3.84 (m, 2H)1 3.45 (q, 2H), 3.35 (t, 2H), 3.07 (s, 6H), 1.57 (s, 3H), 1.25(t, 3H).
Example 2. Synthesis of N-ethyl-N,N-dimethyl-2- hydroxyethylammonium propionate (1131)
According to example 1 , an aqueous solution of N-ethyl-N,N-dimethyl-2- hydroxyethylammonium hydroxide (225 ml) is reacted with 11 ml propionic acid. After distillation of the solvent, 28 g N-ethyl-N,N-dimethyl-2-hydroxy- ethylammonium propionate of a clear liquid is obtained.
1 H NMR (d6-DMSO): δ = 3.82 (m, 2H), 3.47 (q, 2H), 3.41 (t, 2H), 3.08 (s, 6H), 1.86 (q, 2H), 1.23 (t, 3H), 0.88 (t, 3H).
Example 3. Synthesis of N-ethyl-N,N-dimethyl-2- hydroxyethylammonium octanonate (1132)
According to example 1 , an aqueous solution of N-ethyl-N,N-dimethyl-2- hydroxyethylammonium hydroxide (225 ml) is reacted with 23 ml octanoic acid. After distillation of the solvent, 47 g N-ethyl-N,N-dimethyl-2-hydroxy- ethylammonium octanonate of a clear liquid is obtained.
1 H NMR (d6-DMSO): δ = 3.84 (m, 2H), 3.44 (q, 2H), 3.40 (t, 2H), 3.06 (s, 6H)1 1.83 (t, 2H), 1.40 (m, 2H), 1.24 (m, 13H), 0.86 (t, 3H).
Example 4. Synthesis of N-ethyl-N,N-dimethyl-2- methoxyethylammonium acetate (1135)
A. Alkylation
15 A solution of 200 ml N.N-dimethylethylamine in 250 mL acetonitrile is mixed with mechanical stirring and heated to 80 0C. To this solution, 282 g 2- bromoethyl-methyl ether are added slowly while stirring and the reaction mixture is stirred for 3 h at 800C.
2Q After 3 h, the reaction composition is mixed with 2,5 L ethylacetate and the product is precipitated. After separation and drying, 343 g of a white solid is obtained.
B. Anion Exchange
47 g silver hydroxide is added to a solution of 80 g N-ethyl-N,N-dimethyl-2- methoxyethylammonium bromide in 80 ml water while stirring. Silver bromide precipitated. The suspension is filtered via Nylonfilter Cap 0,45 μm
OU and 56 g of a slightly yellow liquid is obtained. C. Neutralisation with Acetic Acid
According to example 1 , the aqueous solution of N-ethyl-N,N-dimethyl-2- methoxyethylammonium hydroxide is reacted with 22 ml of acetic acid. After distillation of the solvent, a clear liquid is obtained.
1H NMR (d6-DMSO): δ = 3.78 (m, 2H)1 3.64 (t, 2H)1 3.52 (q, 2H)1 3.32 (s,
3H), 3.14 (S, 6H), 1.72 (s, 3H), 1.26 (t, 3H).
Example 5. Synthesis of N-ethyl-N,N-dimethyl-2- methoxyethylammonium octanonate (1137)
According to example 1 , the aqueous solution of N-ethyl-N,N-dimethyl-2- methoxyethylammonium hydroxide is reacted with 26 ml of octanoic acid. After distillation of the solvent, 46 g of a clear liquid N-ethyl-N,N-dimethyl-2- methoxyethylammonium octanonate is obtained.
1H NMR (d6-DMSO): δ = 3,74 (m, 2H), 3,54 (t, 2H), 3,42 (q, 2H), 3,31 (s,
3H), 3,05 (s, 6H), 1 ,75 (t, 2H), 1 ,37 (m, 2H), 1 ,24 (m, 13H), 0,87 (t, 3H).
Example 6:
Antimicrobial efficacy was tested using the following challenge testing procedure: The challenge testing procedure consists in challenging a non- contaminated antimicrobial product according to the invention with a prescribed inoculum of suitable microorganisms and storing the inoculated product at a prescribed temperature, e.g. room temperature. The number of organisms surviving in the test products is determined at specified intervals of time.
According to the description given in the European pharmacopea (Ph.Eur.5 Ausgabe, Grundwerk 2005, §5.1.3), the challenge tests are done following the procedure given thereafter. Production of the inoculum
A fresh stock culture of the specific micro-organsisms is inoculated on the surface of Agar medium B for bacteria and on the surface of Agar medium C for fungi. The bacteria culture will be incubated until sufficient sporulation (18-24h at 30-350C) In order to harvest the bacteria, the surface of the Agar media is washed out with a sterile solution containing sodium chloride (9 g/l) and poured into an adequate vessel. The concentration of germs in the suspension will be adjusted with the same solution to a concentration close to 108 micro-organism/ ml. Immediately after that action, a sample of this suspension is taken and the germ concentration in CFU/ml will be measured using the method of membran filtration or counting on Agar plate. This determines the value of the inoculum. The suspension must be used immediately.
Method of determination of germ count In order to determine the number of micro-organisms in the inoculated preparation (containing also the antimicrobial product according to invention), the same Agar medium as for the preparation of the inoculum will be used.
The aqueous suspension/solution containing 1 % of the used ionic liquids (= verum) is inoculated with a suspension of the tests micro-organisms (in our case Pseudomonas aeruginosa or Escherichia coli or Staphylococcus aureus or Candida albicans or Malassezia furfur or Staphylococcus epidermidis or Propionibacterium acnes or Corynebacterium xerosis) in such a way that a concentration from 105 to 106 microorganism/ml of the preparation is reached. The inoculated volume should not be above 1% v/v of the overall test solution. The suspension will be mixed in order to get a good homogenisation.
Water alone (= placebo) is treated in the same way. Antimicrobial activity of the verum will be detected once the survival rate of a microorganism for the verum is significantely lower than for the placebo.
The inoculated preparation is stored away from the daylight at 20-25 0C. In order to begin the test, 1 g or 1 ml samples from the tests preparation (containing the inoculated micro-organsisms and the antimicrobial product according to the invention) will be taken at different intervals of time (in our case , 0, 2 min, 5 min, 30 min, 1h, 3h, 6h, 24h, 48h, 7 days, 14 days and 28 days) and the number of microorganisms will be measured using the Agar plate or the membrane filtration method. It is important to make sure that any remaining antimicrobial activity to be eliminated by dilution, filtration or specific inactivation.
Results:
N-ethyl-N,N-dimethyl-2-methoxyethylammonium octanoate = 1137 N-ethyl-N,N-dimethyl-2-hydroxyethylammonium octanoate = 1132
Both compounds show a unique antimicrobial activity as documented in the following tables with different organisms (the 1st part of each individual table represents the total number of microorganisms versus incubation time at linear scale, the 2nd part at log-scale).:
Escherichia co/i
Placebo Water 1132 [1.0%] 1137 [1.0%]
Oh 140000 100 0 1h 180000 200 0
3h 180000 0 0
6h 100000 0 0
24h 87000 0 0
Placebo Water 1132 11.0%] 1137 11.0%]
Oh 5,1 2,0
1 h 5,3 2,3
3h 5,3
6h 5,0
24h 4.9
Pseudomonas aeruginosa
Placebo Water 1132 [1.0%] 1137 [1.0%]
Oh 170000 100 0
1 h 120000 100 0
3h 81000 0 0
6h 72000 0 0
24h 89000 0 0
Placebo Water 1132 [1.0%] 1137 [1.0%]
Oh 5,2 2,0
1 h 5,1 2,0
3h 4,9
6h 4,9
24h 4,9
Figure 1 visualizes this table.
Staphylococcus aureus
Placebo Water 1132 [1.0%] 1137 [1.0%]
Oh 210000 100 0
1 h 180000 0 0
3h 200000 0 0
6h 87000 0 0
24h 48000
Placebo Water 1132 [1.0%] 1137 [1.0%]
Oh 5,3 2,0
1 h 5,3
3h 5,3 6h 4,9
24h 4,7
Candida albicans
Placebo Water 1132 [1.0%] 1137 [1.0%]
Oh 170000 100 0
1h 160000 0 0
3h 180000 0 0
6h 170000 0 0
24h 190000 0 0
10 Placebo Water 1132 [1.0%] 1137 [1.0%]
Oh 5,2 2,0
1 h 5,2
3h 5,3
6h 5,2
24h 5,3
-15 Figure 2 visualizes this table.
Malassezia furfur
Placebo Water 1132 [1.0%] 1137 [1.0%]
Oh 56000 0 0
1h 46000 0 0
20 3h 68000 0 0
6h 43000 0 0
24h 36000 0 0
Placebo Water 1132 [1.0%] 1137 [1.0%]
Oh 4,7
25 1 h 4,7
3h 4,8
6h 4.6
24h 4,6
Figure 3 viszalizes this table.
on oυ Staphylococcus epidβmtidis
Placebo Water 1132 [1.0%] 1137 [1.0%]
Oh 160000 0 0 1 h 150000 0 0
3h 190000 0 0
6h 120000 0 0
24h 770000 0 0
Placebo Water 1132 11.0%] 1137 11.0%]
Oh 5,2
1 h 5,2
3h 5,3
6h 5,1
24h 5,9
Propionibacterium acnes
Placebo Water 1132 [1.0%] 1137 [1.0%]
Oh 180000 0 0
1h 160000 0 0
3h 160000 0 0
6h 150000 0 0
24h 100 0 0
Placebo Water 1132 [1.0%] 1137 [1.0%]
Oh 5,3
1h 5,2
3h 5,2
6h 5,2 24h 2.0
Corynebactβrium xerosis
Placebo Water 1132 [1.0%] 1137 [1.0%]
Oh 83000 0 0
1 h 17000 0 0
3h 2900 0 0
6h 600 0 0
24h 0 0 0
Placebo Water 1132 [1.0%] 1137 [1.0%]
Oh 4,9
1 h 4,2
3h 3,5
6h 2,8
24h N-ethyl-N,N-dimethyl-2-methoxyethylammonium acetate = 1135 N-ethyl-N,N-dimethyl-2-hydroxyethylammonium acetate = 1130 N-ethyl-N,N-dimethyl-2-hydroxyethylammonium propionate = 1131
Three compounds show an antimicrobial activity as documented in the following tables with different organisms (the 1st part of each individual table represents the total number of microorganisms versus incubation time at linear scale, the 2nd part at log-scale).:
Pseudomonas aeruginosa
Placebo Water 1130 [1.0%] 1131 [1.0%]
Oh 170000 70000 70000
1h 120000 51000 53000
3h 81000 13000 12000
6h 72000 2900 7100
24h 89000 0 0
PlaceboWater 1130 [1.0%] 1131 [1.0%]
Oh 5,2 4,8 4,8
1h 5,1 4,7 4,7
3h 4,9 4,1 4,1
6h 4,9 3,5 3,9
24h 4.9
Staphylococcus epidermidis
Placebo Water 1130 [1.0%] 1131 [1.0%]
Oh 160000 140000 600
1h 150000 150000 6400
3h 190000 120000 240000
6h 120000 160000 230000
24h 770000 81000 55000
Placebo Water 1130 [1.0%] 1131 [1.0%]
Oh 5,2 5,1 2,8
1h 5,2 5,2 3,8 3h 5,3 5,1 5,4
6h 5,1 5,2 5,4
24h 5,9 4,9 4,7
Pseudomonas aeruginosa
Placebo Water 113511.0%]
Oh 170000 80000
1h 120000 57000
3h 81000 9200
6h 72000 1100
24h 89000 0
Placebo Water 1135[1.0%]
Oh 5,2 4,9
1h 5,1 4,8
3h 4,9 4,0
6h 4,9 3,0
24h 4,9
Staphylococcus epidermidis
Placebo Water 1135 [1.0%]
Oh 160000 200000
1h 150000 200000
3h 190000 190000
6h 120000 100000
24h 770000 46000
Placebo Water 1135 [1.0%]
Oh 5,2 5,3
1h 5,2 5,3
3h 5,3 5,3
6h 5,1 5,0
24h 5,9 4,7 Application examples:
A) Roll-on formulation
The above formulation A or B may of course contain one or more actives among the following list: Triethyl Citrate, Aluminium Chlorohydrate, Ethylhexylglycerol, Farnesol, Polyaminopropyl Biguanide, Aluminium Circonium .Tetrachlorohydrex GLY, Pentetic Acid, Diisopropylamine Aminoethylpropanol, Zinc Ricinoleate, aluminium salts, Lactic Acid, Triclosan. C) Waterproof suncare spray [amounts are given in % by weight of the formulation]
Procedure: phase A will be mixed at room temperature. Phase B will be mixed at room temperature and will be given to phase A while stirring.
The above formulation may of course contain one or more actives among the following list: Myrtrimonium Bromid, Lactic Acid, Chlorohexidine Digluconate, Salicylic Acid, Phenoxyisopropanol, Isopropanol, Farnesol, Glycolic Acid, Tannic acid, Sulfur, Alcohol, Triclosan, Zinc Gluconate, Zinc PCA, Camphor, Aluminium salts, Sodium Lactate, Polyaminopropyl Biguanide, Zinc Acetat. Zinc Pyrithion, Piroctone Olamine, Ketocokanzole, Tropolone, Hinokitol, Selenium Sulfide, Climbazole, Sodium Salicylate, Ciclopiroxolamine, Neem, Basilic oil, lchtammol, Melaleuca Alternifolia, , Centaurea Cyanus, Melia Azadirachta, Sulfur , Clotrimazole, Crotamiton, Zinc Salicylate, Selenium Sulfide, Tussilago farfara, Arctium lappa, Piroctone Olamine, Salicylic Acid, ,Zinc Sulfate, Rosmarinus officinalis, Ketoconazole.
D) Pump hairspray [amounts are given in % by weight of the formulation]:
Procedure: Phase B is given to phase A while stirring. Phase C is mixed and added to the combined phases A and B. Stirring until homogeneity.
The above formulation may of course contain one or more actives among the following list:
Zinc Pyrithione, Piroctone Olamine, Ketoconazole, Tropolone, Hinokitol Selenium Sulfide, Salicylic Acid, Climbazole, Sodium Salicylate, Ciclopiroxolamine, Neem, Basilic oil, lchtammol, Melaleuca Alternifolia, Centaurea Cyanus, Melia Azadirachta, Farnesol, Sulfur, Clotrimazole, Crotamiton, Zinc Salicylate, Tussilago farfara, Arctium lappa, Zinc Sulfate, Rosmarinus officinalis, Ketoconazole.
The above formulation may of course contain one or more actives among the following list:
Zinc Pyrithione, Piroctone Olamine, Ketoconazole, Tropolone, Hinokitol, Selenium Sulfide, Salicylic Acid, Climbazole, Sodium Salicylate, Ciclopiroxolamine, Neem, Basilic oil, lchtammol, Melaleuca Alternifolia, Centaurea Cyanus,, Melia Azadirachta, Farnesol, Sulfur , Clotrimazole, , Crotamiton, Zinc Salicylate, Tussilago farfara, Arctium lappa, Zinc Sulfate, Rosmarinus officinalis, Myrtrimonium Bromid, Lactic Acid, Chlorohexidine Digluconate, Phenoxyisopropanol, Isopropanol, Farnesol, Glycolic Acid, Tannic acid, Alcohol, Triclosan, Zinc Gluconate, Zinc PCA, Camphor, Aluminium salts, Sodium Lactate,, Polyaminopropyl Biguanide,, Zinc Acetat,, Triethyl Citrate, Ethylhexylglycerol, , Aluminium Circonium , Tetrachlorohydrex GLY, Pentetic Acid, Diisopropylamine Aminoethylpropanol, Zinc Ricinoleate, Aluminium Sesquichlorohydrate, Lactic Acid, Triclosan.
F) hair care formulation [amounts are given in % by weight of the formulation)
Ingredient B D
Table of figures:
Figure 1 : Summary of results in log scale for 1132 and 1137 against
Pseudomonas aeruginosae
Figure 2: : Summary of results in log scale for 1132 and 1137 against
Candida albicans Figure 3: Summary of results in log scale for 1132 and 1137 against
Malassezia furfur.

Claims

Patent claims
1. Compounds of the formula I in which
R is alkoxymethyl or alkoxyethyl in which the alkoxy group is linear or branched and has 1 to 4 C atoms, hydroxymethyl, hydroxyethyl, hydroxypropyl or hydroxybutyl,
R1 to R3 are independantly of each other linear or branched alkyl with 1 to 4 C atoms,
R4 is linear or branched alkyl with 5 to 11 C atoms, wherein the compound N,N,N-trimethyl-2-hydroxyethylammonium hexanoate is excluded.
2. Compounds according to claim 1 in which R is methoxyethyl, ethoxyethyl or hydroxyethyl.
3. Compounds according to claim 1 or 2 in which R4 is linear alkyl with 5 to 11 C atoms.
4. Compounds according to one or more of claims 1 to 3
N-ethyl-N,N-dimethyl-2-methoxyethylammonium hexanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium hexanoate, N-ethyl-N,N-dimethyl-2-methoxyethylammonium octanoate, N-ethyl-N,N-dimethyl-2-methoxyethylammonium decanoate
N-ethyl-N,N-dimethyl-2-methoxyethylammonium dodecanoate, N-ethyl-N,N-dimethyl-2-hydroxyethylammonium hexanoate, N-ethyl-N,N-dimethyl-3-hydroxypropylammonium hexanoate, N-ethyl-N,N-dimethyl-4-hydroxybutylammonium hexanoate, N-ethyl-N,N-dimethyl-2-hydroxyethylammonium octanoate,
N-ethyl-N,N-dimethyl-2-hydroxyethylammonium decanoate N-ethyl-N,N-dimethyl-2-hydroxyethylammonium dodecanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium hexanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium octanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium decanoate, N-ethyl-N,N-dimethyl-2-ethoxyethylammonium dodecanoate, N,N-diethyl-N -methyl-2-methoxyethylammonium hexanoate,
N,N-diethyl-N -methyl-2-methoxyethylammonium octanoate, N,N-diethyl-N -methyl-2-methoxyethylammonium decanoate N,N-diethyl-N -methyl-2-methoxyethylammonium dodecanoate, N,N-diethyl-N -methyl-2-hydroxyethylammonium hexanoate, N,N-diethyl-N -methyl-2-hydroxyethylammonium octanoate,
N,N-diethyl-N -methyl-2-hydroxyethylammonium decanoate N,N-diethyl-N -methyl-2-hydroxyethylammonium dodecanoate, N,N-diethyl-N -methyl-2-ethoxyethylammonium hexanoate, N,N-diethyl-N -methyl-2-ethoxyethylammonium octanoate, N,N-diethyl-N -methyl-2-ethoxyethylammonium decanoate,
N,N-diethyl-N -methyl-2-ethoxyethylammonium dodecanoate, N1N, N-triethyl-2-ethoxyethylammonium hexanoate, N,N,N-triethyl-2-methoxyethylammonium hexanoate, N,N,N-triethyl-2-hydroxyethylammonium hexanoate, N,N,N-trimethyl-2-hydroxyethylammonium octanoate
N-ethyl-N,N-dimethyl-2-ethoxyethylammonium heptanoate, N-ethyl-N,N-dimethyl-2-methoxyethylammonium heptanoate, N,N-diethyl-N-methyl-2-methoxyethylammonium heptanoate, N,N-diethyl-N-methyl-2-ethoxyethylammonium heptanoate, N,N,N-triethyl-2-ethoxyethylammonium heptanoate,
N,N,N-triethyl-2-methoxyethylammonium heptanoate, N1N, N-trimethyl-2-ethoxyethylammonium heptanoate.
5. Process for the production of compounds according to claims 1 to 4 in which ammonium halides of formula Il
[NRR1R2R3J+ [Hal]" II, in which Hal is Cl, Br or I and R, R1 to R3 has a meaning according to one of claims 1 to 4, are converted to hydroxides via ion exchange followed by reaction with the acid R4-COOH, in which R4 has a meaning according to one of claims 1 to 4.
6. Composition comprising at least one compound of formula I according to one or more of claims 1 to 4.
10 7. Composition according to claim 6 characterized in that the composition is in the form of solutions, suspensions, emulsions, pastes, ointments, gels, creams, lotions, powders, oils, waxes, pencils, shampoos, deodorants-creames, gels, deodorant sticks, roll-ons, aerosols, sprays, pump sprays or lacquers.
15
8. Composition according to claim 6 characterized in that the composition is in the form of cosmetic formulations, medicinal products, paints, inks, home care products, animal care products, products for personal and work hygiene, contact lenses, chromatography materials, medical 20 equipment, protective topicals, lacquers, textiles, coatings and/or plastics.
9. Process for the preparation of a composition according to one or more of claims 6 to 8, characterised in that at least one compound according
^1- to one or more of Claims 1 to 3 is mixed with a carrier and optionally with further active compounds or auxiliaries.
10. Use of compounds according to one or more of claims 1 to 4 as biocides.
30
11. Use of the compounds
N-ethyl-N,N-dimethyl-2-methoxyethylammonium acetate, N-ethyl-N,N-dimethyl-2-hydroxyethylammonium acetate, N-ethyl-N,N-dimethyl-2-hydroxyethylammonium propionate as antibiotics.
12. N-ethyl-N,N-dimethyl-2-methoxyethylammonium acetate, N-ethyl-N,N-dimethyl-2-hydroxyethylammonium propionate.
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US5691440A (en) * 1995-10-05 1997-11-25 Arco Chemical Technonogy, L.P. Catalyst and process for producing isocyanate trimers
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