NO873080L - MICROBICID PREPARATION. - Google Patents

Description

The invention relates to a microbicide preparation and its use for skin and hand disinfection as well as for the disinfection of hard surfaces.

Known hand disinfectants, which as a microbicide active substance, for example contain hexachlorophene, p-chloro-o-benzylphenol, o-phenylphenol, p-chloro-m-xylenol, 2,4-dichlorobenzyl alcohol, polyvinylpyrrolidone-iodine complex, betaine, quaternary ammonium compound ser , chlorhexidine salts , zinc pyridine thione etc., generally have either a higher necessary active substance concentration and/or a narrower spectrum of action and/or an unfavorable skin tolerance and/or a weaker skin affinity.

According to Ullmann 10, 31, the average pH value of normal skin is 5.2, for the skin of the hand 4.5. When washing, the pH value increases, depending on the detergent, more or less markedly. As H. Tonnier, G. Schuster and H. Modde in Arch, klin. exptl. Derm. 221, 232 (1965) reports, today, taking into account the rapid restoration of the normal skin pH value, a certain alkalinity is taken into account, when drying is therefore limited. However, this should apply to normal skin and to detergents, which are used 2-3 times per day. day, as the alkalinity leads to maceration processes, which further promote bacterial growth, because most pathogenic germs prefer an alkaline environment [compare E.Keining, Åerztliche Praxis, 21, No. 103, 5788-5794 (1969)].

Even more unfavorable is the effect of soaps or sinful skin cleansers with disinfectant additives, which can be used up to 20-50 times a day. These effects are also amplified when the cleaning agent contains alcohols such as e.g. ethyl alcohol, n-propyl alcohol or isopropyl alcohol or their mixtures, as thereby the neutralization time is significantly extended [compare W. Schneider, Therapiewoche, 16 675-679 (1968)].

In many cases, it was not immediately possible to produce halogenated hydroxydiphenyl ether-containing liquid microbicide agents with a skin-friendly pH value below 7 without the active substance secreting under the simultaneous influence of the activity. In order to keep the active substance in solution, it was therefore necessary either to use larger quantities of a mono- or divalent alkanol such as ethyl, n-propyl, isopropyl alcohol or propylene glycol or to use significantly higher surfactant concentrations or expensive amphoteric surfactants or betaines.

It has also been shown that, for example, halogenated hydroxydiphenyl ether-containing skin cleansers resp. -disinfectants, which at pH values of 7.2-7.8 are effective against gram-positive and gram-negative bacteria, become ineffective at a pH value of 5.5 at least against some gram-negative germs such as e.g. Escherichia coli or Pseudomonas aeruginosa.

Microbicidal preparations have now been found which can be used for skin and hand disinfection and which do not have the listed disadvantages and have a skin-friendly pH value of 5.0-5.5.

The invention therefore relates to a microbicide preparation which is characterized by the fact that it contains

a) 0.1 - 2.5 wt-# of a microbicide active substance,

b) 0 - 10 wt-# of an aryl or aryloxy-C2-C4-alkanol,

c) 0 - 20 wt-# of an anionic surfactant,

d) 0 - 10 wt-# of a zwitterionic and amphoteric surfactant,

e) 0 - 3 wt-# of a non-ionic surfactant,

f) 0 - 15 wt-# of a dihydric alcohol,

g) 0 - 10 wt-# of a C8-C12-<fe>tt acid»

h) 1 - 25 weight-# of solubility-improving additives,

i) 4.5 - 98.9 wt-# deionized water.

The microbicidal preparations according to the invention can have a pH value of 3.0-9.0 and in addition contain usual thickening and clouding agents.

The microbicidal preparations according to the invention can be used against gram-positive and gram-negative bacteria as well as other organisms such as yeast, fungi, viruses and algae.

A further object of the invention is the use of such a preparation for skin and hand disinfection as well as for the disinfection of solid surfaces.

As component a), the following microbicidal active substances can be used:

(A) compounds of the general formula

in which

R 1 means hydrogen, hydroxy, C 1 -C 4 alkyl, chlorine, nitro,

phenyl or benzyl,

R 2 means hydrogen, hydroxy, C 1 -C 2 -alkyl or chlorine,

R3 means hydrogen, C1-C4-alkyl, hydroxy, chlorine, nitro or a sulfo group in the form of its alkali metal or ammonium salt,

R 4 means hydrogen or methyl and

R5 means hydrogen or nitro.

Such compounds are e.g. phenol, chlorophenol, (o-, m-, p-), 2,4-dichlorophenol, p-nitrophenol, picric acid, xylenol, p-chloro-m-xylenol, cresols (o-, m-, p-), p -chloro-m-cresol, pyrocatechin, resorcin, orcin, 4-n-hexylresorcin, pyrogallol, phloroglucin, carvacrol, thymol, p-chlorothymol, o-phenylphenol, o-benzylphenol, p-chloro-o-benzylphenol and 4-phenolsulfonic acid .

(B) Compounds with the general formula

in which

X means sulfur or the methylene group,

Ri and Ri t mean hydroxy and

<R>2»<R>2» R3» R3» R4»R4»R5 and R5 independently mean hydrogen or chlorine.

Compounds of this formula are e.g. hexachlorophene, tetrachlorophene, dichlorophene, 2,3-dihydroxy-5,5'-dichlorodiphenyl sulfide, 2,2'-dihydroxy-3,3',5,5'-tetrachlorodiphenyl sulfide, 2,2'-dihydroxy-3, 3',5,5',6,6'-hexachlorodiphenylsulfide and 3,3'-dibromo-5,5*-dichloro-2,2*-dihydroxydiphenylmethane,

(C) compounds of the general formula

in which

R 1 , R 2 , R 3 , R 4 and R 5 independently of each other mean hydrogen or chlorine.

Compounds of this formula are e.g. benzyl alcohol, 2,4-, 3,5- or 2,6-dichlorobenzyl alcohol and trichlorobenzyl alcohol,

(D) chlorhexidine and its salts with organic and inorganic acids, (E) Ci2-C;L4-Alkylbetaines and Cg-C^g fatty acid amidoalkyl betaines such as coconut fatty acid amidopropyl betaine, (F) amphoteric surfactants such as e.g. C12-C18-alkylam:1-no» cl~c3~alkanecarboxylic acids, e.g. alkylaminoacetic acids or alkylaminopropionic acids,

(G) zinc pyridine thione and

(H) preferably hydroxydiphenyl ethers of formula

wherein R{ means hydrobranch or hydroxy and R2, R2 > ^''$4' R4°9

R 5 independently of each other means hydrogen or chlorine and preferably in which R 2 and R 3 mean chlorine and R 2 , R 4 , R 4 and R 5 mean hydrogen. Particularly preferred as a compound of formula (4) is 2,4,4'-trichloro-2'-hydroxydiphenyl ether.

The microbicidal active substances can be used individually or in a mixture with each other, i.e. from the same or from different classes. This also applies to components c), d) and

e)-

As component b) mention should be made of aryl or aryloxy-C2-C4~

alkanols with preferably an unsubstituted aryl residue and a linear alkylene residue. Preference is given to 2-phenylethanol and

phenoxyethanol, 3-phenoxypropanol and 4-phenoxybutanol. 2-phenoxyethanol is particularly preferred.

As component c) of the agent according to the invention, sarcosinates, sulfated surfactants, e.g. alkyl sulfates, alkyl ether sulfates, alkyl amide sulfates, alkyl amide ether sulfates, alkyl aryl polyether sulfates or monoglyceride sulfates, sulfonates, e.g. alkylsulfonates, alkylamidesulfonates, alkylarylsulfonates, c-olefinsulfonates or sulfonic acids in water, e.g. alkylsulfosuccinates, alkyl ethersulfosuccinates, or alkylsulfosuccinamide derivatives, further also the acids tyltaurides, alkyl isothionates, fatty acid polypeptide condensation products and fatty alcohol phosphoric acid esters. The alkyl radicals occurring in these compounds preferably have 8 to 24 C atoms.

These anionic surfactants are usually used in the form of their water-soluble salts, such as alkali metal, especially sodium

or potassium or

wherein Rlt<R>2 and R3

independently of each other means hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -hydroxyalkyl. Preferred are C 8 -C 24 alkyl sulfates in the form of their C 1 -C 4 alkanolamine salts, especially monoethanolamine lauryl sulfate.

As zwitterionic and amphoteric surfactants for component d) come into consideration Cg-C^g-<b>etalnes, Cg-c^g-<s>ulfobeta-ines, Cg-C24-alkylamido-Ci-C4-alkylenebetaine, imidazolinecarb -oxylates and N-alkyl-p-amino- or iminopropionates, with<C>1Q-<C>20-alkylamido_C1-C4-alkylene betaines and especially coconut fatty acid amidopropyl betaine being preferred.

As component e) usable non-ionic surfactants are e.g. polypropylene glycol ethoxylates with a molecular weight of 1,000 to 15,000, fatty acid glycol partial esters, e.g. diethylene glycol monostearate, fatty acid alkanolamides and -dialkanolamides, fatty acid alkyl olamide oxylates and fatty amine oxides. Preference is given to the acid alkanolamides and -dialkanolamides and especially coconut fatty acid diethanolamide.

As component f), dihydric alcohols come into consideration, especially those with 2 to 6 C atoms in the alkylene part such as ethylene glycol, 1,2- or 1,3-propanediol, 1,3-, 1,4- or 2,3-butanediol , 1,5-pentanediol and 1,6-hexanediol. Preferred is 1,2-propanediol (propylene glycol). They can be used individually or in combination with each other.

As component g) it is possible to mention saturated and unsaturated C2-C12 fatty acids, such as acetic, propionic, butyric, isovaleric, caproic, caprylic, capric, undecylenic and lauric acids, preferably capric and the undecylenic acid.

As component h) the following compounds come into consideration: Sulfonates of terpenoids or mono- or dinuclear aromatic compounds, e.g. the sulphonates of camphor, toluene, xylene, cumene and naphthol. These sulfonates are in the form of their water-soluble salts, such as the alkali metal, especially sodium or potassium salts or amine(NRiR2R3) salts, wherein R^, R2 and R3 independently of each other mean hydrogen, C^-Cs-alkyl, Cg-Cg -alkenyl, C1-C8-hydroxyalkyl, C5-C8-cycloalkyl or polyalkyleneoxy-C-L-C-Lg-alkyl or R^, R2 and R3 together with the nitrogen atom to which they are attached morpholino or with C-^-C^-alkyl substituted morpholino,

aliphatic saturated or unsaturated Ci4-C2ø monocarboxylic acids, such as myristic, palmitic, stearic, araquine, decyclene, dodecylene, palmitoleic, oleic, ricinol, linoleic, linolenic, eleostearic , arachidonic and 5-eicosenoic acid,

saturated or unsaturated C3-C12 di- or polycarboxylic acids, e.g. malonic, succinic, glutaric, adipic, pimelilnic, corkic, azelalic and sebacic acids, undecanoic and dodecanedicarboxylic acids, fumaric, maleic, tartaric and malic acids as well as citric and aconitic acids,

aminocarboxylic acids, such as ethylenediaminetetraacetic acid,

hydroxyethylethylenediaminetetraacetic acid and nitrilotriacetic acid,

cycloaliphatic carboxylic acids such as camphoric acid,

aromatic carboxylic acids, such as benzene, phenylacetic,

phenoxyacetic and cinnamic acid, salicylic acid, 3-hydroxy- and 4-hydroxybenzoic acid, anisic acid, as well as o-, m- and p-chlorophenylacetic acid as well as o-, m- and p-chlorophenoxyacetic acid,

alkali metal and amine salts of inorganic acids, such as sodium, potassium and amine (NR;LR2R3 ) salts of hydrochloric acid, sulfuric acid, phosphoric acid, C-L-C-LQ-alkylphosphoric acid and boric acid, where RlfR2 and R3 have the above meaning,

isethionic acid

tannic acid

acid amides of formula

wherein R 1 means hydrogen or C-L-C-^-alkyl°S ^2°S R 3 independently of each other means hydrogen, C^-C^2-alkyl, C2-<C>12~alkeny1»Ci-C^-hydroxyalkyl» C2~ cl2 ~ hydroxyalkenyl or a polyglycol ether chain with 1 to 30 groups -CH2-CH2-0- or -CHY1-CHY2-0-,

in which of Y^ and Y2 one is hydrogen and the other is methyl, such as N-methylacetamide,

urea derivatives with formula

wherein R 1 , R 2 , R 3 and R 4 are independently hydrogen, C 1 -C 8 alkyl, C 2 -C 3 alkenyl, C 1 -C 8 hydroxyalkyl or C 2 -C 8 hydroxyalkenyl,

monohydric aliphatic and monocyclic alcohols, such as C 2 -C 8 alkanols, C 2 -C 8 -alkenols and terpene alcohols, e.g. ethanol, propanol, isopropanol, hexanol, cis-3-hexen-l-ol, trans-2-hexen-l-ol, l-octen-3-ol, heptanol, octanol, trans-2-cis-6-nonadien- l-ol, decanol, linalool, geraniol, dihydroterpineol, myrcenol, nopol and terpineol,

aromatic alcohols of formula

in which X means -(CH^-j^T, -CH=CH-CH2- or -O-(CH2 )2_6 and R±, R2 and R3 independently of each other mean hydrogen, hydroxy, halogen or C^-C^-alkoxy, such as benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenylethanol, phenoxyethanol and cinnamic alcohol, polyvalent, optionally alkylated, preferably ethoxylated or/and propoxylated alcohols and their ethers and esters of the general formula

in which

R 1 and R 2 independently of each other mean hydrogen, C 1 -C 12 alkyl,

C2-C12-alkenyl >

wherein R3 means hydrogen -alkyl or C2-<C>12-alkenyl and R4 means hydrogen or CH3-, and X means C2-C-Lo-alkylene or -alkenylene,

The mentioned compounds can be used individually or in a mixture with each other, i.e. from the same or different classes.

The production of the microbicidal preparations according to the invention can take place in a manner known per se, e.g. by dissolving component a) in component h) while adding the other components to the formed solution or by dissolving component a) in component f) and adding the other components to the formed solution.

The thus formed microbicidal preparations according to the invention can be applied to these for disinfection of skin and hands as well as hard surfaces from formulations and, depending on the type of the desired application, diluted or undiluted.

Preferred preparations according to the invention contain

0.1 - 2.5 wt-56 of component a),

0 - 20 weight-56 of component c),

0 - 10 wt-56 of component d),

0 - 15 weight-56 of component f),

1 - 7 weight of component g),

1 - 25 weight-# of component h) and

20.5 - 97.9 wt-56 deionized water.

A particularly preferred preparation according to the invention contains as component a) p-chloro-m-xylenol and as component

b) 1-phenoxy-2-propanol in the weight ratio 1:2 to 1:3.

As obscurity resp. pearlescent agents can possibly do so

common additives are added, such as ethylene glycol distearate, monostearate, glycerol monostearate and polystyrene latex.

Cellulose derivatives, such as cellulose ethers, fatty acid alcohol amides, guar derivatives, MgAl silicates or glucamates can be used as thickeners.

The invention shall be explained with the help of some examples, where percentages and parts are weight # or weight parts.

Example 1

In 5 parts of sodium cumene sulphonate, in the form of a 40% aqueous solution, dissolve 2.0 parts of 2,4,4'-trichloro-2'-hydroxydiphenyl ether. The clear solution is heated to 40°C and mixed with constant stirring with 12.0 parts of monoethanolamine-lauryl sulfate in the form of a 30# aqueous solution, 3.0 parts of coconut fatty acid amidopropyl betaine, 5.0 parts of propylene glycol, 1.0 parts of capric acid and 0.3 parts of a polystyrene latex for drying. Stir for another 10 minutes and then mix the solution with deionized water up to a total of 100 parts (36.2 parts water). You get a pulpy solution, the pH value of which is adjusted to 5-5.5 with citric acid or caustic soda, and which is very effective against gram-positive and gram-negative bacteria, yeast and fungi.

Example 2

In 5 parts of sodium cumene sulphonate, in the form of a 40% aqueous solution, dissolve 2.0 parts of 2,4,4'-trichloro-2'-hydroxydiphenyl ether. The clear solution is heated to 40°C and mixed with constant stirring with 12.0 parts of monoethanolamide-lauryl sulfate, in the form of a 30# aqueous solution, 3.0 parts of coconut fatty acid amidopropyl betaine, 5.0 parts of propylene glycol, 2.0 parts undecylenic acid and 0.3 parts of a polystyrene latex. Stir for another 10 minutes and then mix the solution with deionized water up to a total of 100 parts (35.2 parts water). You get a pulpy solution, the pH value of which is set to 5-5.5, which is very effective against gram-positive and gram-negative bacteria, yeast and fungi. Aqueous citric acid or baking soda solutions can be used as needed to adjust the pH value.

You proceed as described in examples 1 and 2, but use the active substances listed in the following table, and you get preparations that work equally well against gram-positive and gram-negative bacteria, yeast and fungi.

Example 24

1 part of 2,4,4'-trichloro-2'-hydroxydiphenyl ether is dissolved in 10 parts of propylene glycol. The clear solution is mixed with 13.35 parts of a 30% aqueous solution of cocoamidopropyl betaine and stirred homogeneously. To this solution, 5 parts of sodium cumene sulphonate (in powder form), 50 parts of deionized water and 8 parts of citric acid monohydrate are added in order, with constant stirring, and stirred homogeneously. A homogeneous suspension is produced. The pH value of the suspension is then adjusted to 5.0 with monoethanolamine and the clear solution supplemented with deionized water to 100 parts.

Example 25

1 part of 2,4,4'-trichloro-2'-hydroxydiphenyl ether is dissolved in 10 parts of propylene glycol. The clear solution is mixed with 6.7 parts of a 30% aqueous solution of cocoamidopropyl betaine and stirred homogeneously. To this solution, 5 parts of sodium cumene sulphonate (in powder form), 50 parts of deionized water and 8 parts of citric acid monohydrate are added in order, with constant stirring, and stirred homogeneously. A homogeneous suspension is obtained. Thereby, the pH value of the suspension is adjusted with monoethanolamine to 5.0 and the clear solution is supplemented with deionized water to 100 parts.

Example 26

1 part of 2,4,4'-trichloro-2'-hydroxydiphenyl ether is dissolved in 10 parts of propylene glycol. The clear solution is heated to 50°C and mixed with constant stirring in sequence with 5 parts of sodium cumulus sulphonate (powder form), 2 parts of a propylene oxide/ethylene oxide block polymer with a molecular weight of 6800, 60 parts of deionized water and 8 parts of citric acid monohydrate and stir homogeneously. A homogeneous suspension is obtained. The pH value of the suspension is then set to 5.0 with monoethanolamine and the clear solution is supplemented with deionized water in a total of 100 parts.

Claims (16)

1. Microbicide preparation, characterized in that it contains a) 0.1 - 2.5 wt-# of a microbicide active substance, b) 0 - 10 wt-# of an aryl or aryloxy-C2 -C4 -alkanol, c) 0 - 20 wt-56 of an anionic surfactant, d) 0 - 10 wt-# of a zwitterionic and amphoteric surfactant, e) 0 - 3 wt-# of a non-ionic surfactant, f) 0 - 15 wt-5é of a dihydric alcohol, g) 0 - 10 wt-£ of a Cg- <C>j^ - <fe> tt acid, h) 1 - 25 weight-$ solubility-improving additives, i) 4.5 - 98.9 wt-56 deionized water. 2. Preparation according to claim 1, characterized in that a hydroxydiphenyl ether with formula is used as component a). wherein % means hydrogen or hydroxy, and R 2 , R 2 , R' 3 » R 4 » R 4 and R 5 independently of each other means hydrogen or chlorine. 3. Preparation according to claim 1, characterized in that as component a) Contains a compound with formula in which R 1 means hydrogen, hydroxy, C 1 -C 4 -alkyl, chlorine, nitro, phenyl or benzyl, Rg means hydrogen, hydroxy, C 1 -C 2 -alkyl or chlorine, R 3 means hydrogen, C 1 -C 3 -alkyl, hydroxy, chlorine, nitro or a sulfo group in the form of their alkali metal or ammonium salt, R 4 means hydrogen or methyl and R5 means hydrogen or nitro. 4. Preparation according to claim 1, characterized in that as component a) it contains a compound of formula in which X means sulfur or the methylene group, Ri and Ri mean hydroxy and <R> g, R2 > R3 > K3. R4» R4. R5 and R5 mean independently of each other hydrogen or chlorine. 5. Preparation according to claim 1, characterized in that as component a) it contains a compound of formula in which R±, R2, R3, R4 and R5 independently of each other mean hydrogen or chlorine. 6. Preparation according to claim 1, characterized in that component a) contains chlorhexidine. 7. Preparation according to one of claims 1 to 6, characterized in that 2-phenoxyethanol is used as component b). 8. Preparation according to one of claims 1 to 7, characterized in that an alkanolamine fatty acid sulfate is used as component c). 9. Preparation according to one of claims 1 to 8, characterized in that a fatty acid amidoalkylene betaine is used as component d). 10. Preparation according to one of claims 1 to 9, characterized in that a fatty acid dialkanolamide is used as component e). 11. Preparation according to one of claims 1 to 10, characterized in that a C₁-C₂ alkylene glycol is used as component f). 12. Preparation according to one of claims 1 to 11, characterized in that a saturated fatty acid is used as component g). 13. Agent according to one of claims 1 to 12, characterized in that the alkali metal or ammonium salts of cumolic, xylene or toluene sulphonic acids are used as component h). 14. Agent according to one of claims 1 to 13, characterized in that it contains 0.1 - 2.5% by weight of component a), 0 - 20% by weight of component c), 0 - 10 wt-# of component d), 0 - 15 weight # of component f) 1 - 7 weight # of component g), 1 - 25 weight-# of component h) and 20.5 - 97.9 wt-lb deionized water. 15. Preparation according to claim 14, characterized by it containing 0.1 - 2.5% by weight of 2,4,4'-trichloro-2'-hydroxydiphenyl ether as component a), 2 - 20 wt # of Na monoethanolamine lauryl sulfate as component c), 0 - 10 wt # coconut fatty acid amidopropyl betaine as component d), 0 - 15 wt-# propylene glycol as component f), 1 - 7 weight # of capric or undecylenic acid as component g) <,> 1 - 25 wt-# Na cumene sulphonate as component h) and 20.5 - 92.9 wt-# deionized water. 16. Use of an agent according to one of claims 1 to 15 for skin and hand disinfection.