Aqueous composition particularly for treating mucous membranes and / or wounds

Abstract

The present invention relates to an aqueous composition, which is particularly useful for treating wounds, comprising a dihydrotriazine compound of the following general formula I or its tautomer or salt thereof, wherein R1 represents (i) phenyl or phenylalkyl, each of which is optionally substituted by 1 to 3 substituents selected from the following: C 1‑6 -alkoxy, hydroxyl, halogen atom, C 1‑6 -Haloalkyl, C 1‑6 -alkyl, sulfonylamino and C 1‑6 ‑halogenated alkoxy, (ii) naphthyl or naphthylalkyl, (iii) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, (iv) an alkyl group having 1 to 16 carbon atoms or (v) a cycloalkyl group or a cycloalkylalkyl group, ‑R1′ represents a hydrogen atom bonded to a nitrogen atom at position 1 or 3 of a dihydrotriazine ring, ‑R2 and R3 independently represent a hydrogen atom or a methyl group, ‑R4 represents an alkyl group having 7 to 16 carbon atoms, and the ‑dashed line represents that the position of the double bond is between positions 1 and 2 or between positions 2 and 3 of the dihydrotriazine ring, and ‑defoaming agent. #imgabs0#Formula I.

Description

[0001] Application areas and existing technologies

[0002] The present invention relates to an aqueous composition which is particularly suitable for treating mucous membranes and / or wounds.

[0003] Iodine-containing products containing iodine in the form of iodophors, such as polyvinylpyrrolidone iodine, have been established for the treatment of mucous membranes and wounds. They are characterized by good tolerability. The use of these agents is limited due to possible allergic and sensitizing effects and due to the known absorption of iodine by the organism.

[0004] For this reason, products having cationic antimicrobial active substances have already been proposed.

[0005] WO 03 / 004013 A1 discloses an aqueous composition comprising polyhexamethylene biguanide, which can be present in particular in the form of a wound rinse or wound gel.

[0006] The subject matter of DE 102 05 883 A1 is aqueous antimicrobial agents based on bispyridinium alkanes.

[0007] WO 2007 / 031520 A2 relates to the use of octenidine dihydrochloride for the preparation of a pharmaceutical composition, in particular for the treatment of wounds.

[0008] A disadvantage of conventional agents is that they are ineffective against fungi, especially yeasts.

[0009] Octenidine-containing preparations are available under the name Octenisept, which, although they can show good mucosal tolerance, can lead to intolerance and even necrosis when used in deeper wounds. This is disclosed, inter alia, by the German Federal Institute for Drugs and Medical Products: ( https: / / www.bfarm.de / SharedDocs / Risikoinformationen / Pharmakovigilanz / DE / RHB / 2011 / rhb-octenisept.html ).

[0010] EP 0 411 315 A1 discloses an octenidine-containing composition.

[0011] Purpose and Solution

[0012] The object of the present invention is to provide a very well tolerated composition which is suitable for the treatment of mucous membranes and / or wounds and which at the same time has an improved antifungal, in particular antiyeast, efficacy.

[0013] According to the invention, this object is achieved by an aqueous composition having the features of independent claim 1. Preferred embodiments of the aqueous composition are subject matter of the dependent claims and the description. The wording of all claims is hereby incorporated into the present description by explicit reference.

[0014] The composition according to the invention is aqueous, ie a composition comprising water. The aqueous composition is preferably in the form of an aqueous solution, ie in the form of a solution comprising water, or in the form of a hydrogel, ie in the form of a gel comprising water.

[0015] The aqueous composition has the following substances:

[0016] - the following dihydrotriazine compound of general formula I or its tautomer, i.e., the tautomer of the dihydrotriazine compound of general formula I, or its salt, in particular, a pharmacologically acceptable salt, i.e., a salt of the dihydrotriazine compound of general formula I, in particular, a pharmacologically acceptable salt:

[0017]

[0018] in

[0019] - R1 represents (i) phenyl or phenylalkyl, each of which is optionally substituted by 1 to 3 substituents selected from the following: 1-6 -alkoxy, hydroxyl, halogen atom, C 1-6 -haloalkyl, C 1-6 -alkyl, sulfonylamino and C 1-6 - a haloalkoxy group, (ii) a naphthyl group or a naphthylalkyl group, (iii) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, (iv) an alkyl group having 1 to 16 carbon atoms or (v) a cycloalkyl group or a cycloalkylalkyl group,

[0020] -R1' represents a hydrogen atom bonded to the nitrogen atom at the 1- or 3-position of the dihydrotriazine ring,

[0021] - R2 and R3 independently represent a hydrogen atom or a methyl group,

[0022] - R4 represents an alkyl group having 7 to 16 carbon atoms, and

[0023] - The dotted line indicates that the double bond is located between the 1 and 2 positions or between the 2 and 3 positions of the dihydrotriazine ring,

[0024] and

[0025] -Defoaming agents.

[0026] The aqueous composition is particularly suitable for preventing, i.e. preventing, or treating mucous membranes and / or wounds, preferably acute or chronic wounds, and / or for preventing, i.e. preventing, or treating infections and / or for preventing, i.e. preventing, or treating infectious diseases, such as erysipelas or erysipelas. Therefore, in the sense of the present invention, the aqueous composition may also be referred to as an aqueous wound treatment composition, in particular an aqueous antibacterial composition. The aqueous composition is preferably an aqueous wound irrigant.

[0027] In the sense of the present invention, the expression "dihydrotriazine compound" is understood to mean a compound having a six-membered triazine ring having only two double bonds, a so-called dihydrotriazine ring, wherein the triazine ring or dihydrotriazine ring has in each case one ring nitrogen atom in the 1-, 3- and 5-positions and in each case one ring carbon atom in the 2-, 4- and 6-positions, and the position of one double bond is between the 4- and 5-positions of the triazine ring or dihydrotriazine ring and the position of the other double bond, the second or remaining double bond, is between the 1- and 2-positions or between the 2- and 3-positions of the triazine ring or dihydrotriazine ring.

[0028] In the sense of the present invention, the expression "defoamer" is understood to mean compounds which are able to slowly attenuate, ie reduce or lower, or to avoid the formation of foam.

[0029] In the sense of the present invention, the expression "surfactant" is understood to mean a compound which reduces the surface tension of a liquid, in particular water or an aqueous liquid, and / or the interfacial tension between two phases and enables or promotes the formation of dispersions and / or acts as a solubilizer.

[0030] In the sense of the present invention, the expression “emulsifier” is understood to mean a compound which is able to mix and in particular stabilize two liquids which are immiscible with one another, such as oil and water, into an emulsion.

[0031] In the sense of the present invention, the expression "fungus" may denote unicellular or multicellular fungi.

[0032] In the sense of the present invention, the expression "yeast" is understood to mean unicellular fungi which reproduce by budding or division (differentiation) (so-called yeast fungi).

[0033] In the sense of the present invention, the expression "phenyl" is understood to mean a benzene radical, ie the atomic group -C6H5.

[0034] In the sense of the present invention, the expression "benzyl" is understood to mean the phenylmethyl group -CH2-C6H5, previously also known as α-tolyl.

[0035] In the sense of the present invention, the expression "phenylalkyl" means a radical in which a straight-chain, i.e. unbranched or branched alkyl or alkylene group, in particular one having 1 to 6 carbon atoms, is bonded to a phenyl group. The alkyl or alkylene group may be substituted or unsubstituted. The phenylalkyl group is preferably benzyl, methylbenzyl, such as in particular 4-methylbenzyl, 1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, 2-phenylpropyl or 3-phenylpropyl.

[0036] The phenyl or phenylalkyl phenyl ring may have 1 to 3 substituents, in particular selected from halogen atoms, hydroxyl groups, C 1-6 -alkyl, C 1-6 -haloalkyl, C1-6 -alkoxy, C 1-6 -haloalkoxy and sulfonylamino.

[0037] In the sense of the present invention, the expression "halogen atom" may denote a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

[0038] In the sense of the present invention, the expression "C 1-6 "-alkyl" may represent a corresponding, i.e., a straight-chain or branched, alkyl group having 1 to 6 carbon atoms. Here, the alkyl group may be a substituted or unsubstituted alkyl group. For example, the C 1-6 -Alkyl can be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n-hexyl or isohexyl.

[0039] In the sense of the present invention, the expression "C 1-6 "-haloalkyl" may especially denote chloromethyl, bromomethyl, 1-chloroethyl or trifluoromethyl.

[0040] In the sense of the present invention, the expression "C 1-6 "-Alkoxy" may in particular denote methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy or isobutoxy.

[0041] In the sense of the present invention, the expression "C 1-6 "-Haloalkoxy" may especially denote trifluoromethoxy.

[0042] In the sense of the present invention, the expression "naphthyl" may denote 1-naphthyl or 2-naphthyl.

[0043] In the sense of the present invention, the expression "naphthylalkyl" means a group in which a straight-chain, i.e. unbranched or branched, alkyl group, in particular an alkyl group having 1 to 6 carbon atoms, is bonded to a naphthyl group. The alkyl group may be substituted or unsubstituted. The naphthylalkyl group is preferably 1-naphthylmethyl, 2-naphthylmethyl, 1-naphthylethyl or 2-naphthylethyl.

[0044] In the sense of the present invention, the expression "heterocyclic group" means a three- to six-membered heterocyclic group comprising 1 to 3 atoms selected from nitrogen atoms, oxygen atoms and sulfur atoms, wherein a benzene ring may be fused or condensed to the heterocyclic group. The heterocyclic group may represent, for example, pyridyl, pyrazinyl, thiazolyl, piperidinyl, piperazinyl, tetrahydrofuranyl, thienyl, pyrrolyl, pyrrolidinyl, oxazolyl, imidazolyl, isoxazolyl, isothiazolyl, pyrazolyl, tetrahydropyranyl, 2-oxotetrahydropyranyl, pyrimidinyl, pyridazinyl (Pyradizinylgruppe), morpholinyl, 1,3,5-triazinyl, 1,2,4-triazinyl, quinolyl or isoquinolyl.

[0045] In particular, a heterocyclic group in the sense of the present invention may represent 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furyl, 2-thiazolyl, 1-piperidinyl, 1-piperazinyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 8-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl or 5-isoquinolyl.

[0046] In the sense of the present invention, the expression "heterocyclic alkyl" means a group in which a straight-chain, i.e. unbranched or branched alkyl group, in particular an alkyl group having 1 to 6 carbon atoms, is bonded to a heterocyclic group, in particular a heterocyclic group as defined or described in the preceding paragraphs. The alkyl group may be substituted or unsubstituted. The heterocyclic alkyl group is preferably 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-pyridylethyl, 3-pyridylethyl, 4-pyridylethyl, pyrazinylmethyl, pyrazinylethyl, 2-furanylmethyl, 2-furanylethyl, 2-thiazolylmethyl, 2-thiazolylethyl, 4-piperidinylmethyl, 2-quinolylmethyl, 3-quinolylmethyl, 4-quinolylmethyl, 5-quinolylmethyl, 8-quinolylmethyl, 1-isoquinolylmethyl, 3-isoquinolylmethyl, 4-isoquinolylmethyl or 5-isoquinolylmethyl.

[0047] In the sense of the present invention, the expression "heterocyclic aminoalkyl" means a group in which a straight-chain, i.e. unbranched or branched, alkyl group, in particular an alkyl group having 1 to 12 carbon atoms, is bonded to a heterocyclic amino group. The alkyl group may be substituted or unsubstituted. The heterocyclic aminoalkyl group is preferably 4-amino-dihydro-1,3,5-triazine-2-yl-amino, 4-alkylamino-dihydro-1,3,5-triazine-2-yl-amino or 4-phenylalkylamino-dihydro-1,3,5-triazine-2-yl-amino.

[0048] In the sense of the present invention, the expression "alkyl radical having 1 to 16 carbon atoms" means a linear, i.e. unbranched or branched, alkyl radical having 1 to 16 carbon atoms. The alkyl radical may be substituted or unsubstituted. The alkyl radical having 1 to 16 carbon atoms is preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-hexyl, n-heptyl, n-octyl, tert-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl or n-hexadecyl.

[0049] In the sense of the present invention, the expression "cycloalkyl" denotes in particular a cycloalkyl radical having 3 to 6 carbon atoms. For example, the cycloalkyl radical may be cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0050] In the sense of the present invention, the expression "cycloalkyl-alkyl" particularly denotes a group in which a straight-chain, i.e. unbranched or branched alkyl group, in particular an alkyl group having 1 to 6 carbon atoms, is bonded to a cycloalkyl group, in particular a cycloalkyl group as defined or described in the preceding paragraph. The alkyl group may be substituted or unsubstituted. The cycloalkylalkyl group is preferably cyclohexylmethyl, 1-cyclohexylethyl or 2-cyclohexylethyl.

[0051] In the sense of the present invention, the expression "alkyl radical having 7 to 16 carbon atoms" means a straight-chain, ie unbranched or branched, alkyl radical having 7 to 16 carbon atoms. The alkyl radical may be a substituted or unsubstituted alkyl radical. The alkyl radical having 7 to 16 carbon atoms is preferably n-heptyl, n-octyl, tert-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl or n-hexadecyl.

[0052] In the sense of the present invention, the expression "salt" used in conjunction with the dihydrotriazine compounds of the general formula I may denote in particular salts with organic acids such as formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutaric acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, ascorbic acid, aspartic acid, glutamic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, benzenesulfonic acid, p-toluenesulfonic acid or methanesulfonic acid.

[0053] In the sense of the present invention, the expression "antimicrobial composition" is understood to mean a composition for reducing microorganisms on living surfaces, in particular on mucous membranes and / or wounds, and / or for preventing, i.e. prophylaxis, or treating mucous membranes and / or wounds and / or for preventing and / or treating infections and / or infectious diseases.

[0054] On the one hand, the present invention is based on the surprising knowledge that, compared to antimicrobial agents of the general type, such as polyhexamethylene biguanide or octenidine hydrochloride, dihydrotriazine compounds of the general formula I or their tautomers or their salts have improved antifungal, in particular antiyeast efficacy. As a result, wounds and / or infections and / or infectious diseases, in particular caused or co-caused by fungi, can be better prevented or treated in a particularly advantageous manner.

[0055] Furthermore, it has surprisingly been found that by combining dihydrotriazine compounds of the general formula I or their tautomers or their salts with defoamers, low-foaming or foam-free compositions can be obtained, thereby optimizing or making possible in the first place the use of dihydrotriazine compounds, in particular for the prevention or treatment of mucous membranes and / or wounds and / or infections and / or infectious diseases. Due to their (sometimes) extreme foaming behavior, it is not desirable to use dihydrotriazine compounds of the general formula I or their tautomers or their salts for the treatment and / or flushing of mucous membranes and / or wounds.

[0056] In one embodiment of the present invention,

[0057] - R1 represents a phenyl group or a phenylalkyl group, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of a fluorine atom, a chlorine atom, a hydroxyl group, a methyl group, a tert-butyl group, a trifluoromethyl group and a methoxy group,

[0058] -R1' represents a hydrogen atom bonded to the nitrogen atom at the 1- or 3-position of the dihydrotriazine ring,

[0059] - R2 and R3 each represent a methyl group and

[0060] -R4 represents n-octyl, n-nonyl or n-decyl.

[0061] Preferably,

[0062] - R1 represents a phenyl group, a benzyl group or a 2-phenylethyl group, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of a fluorine atom, a chlorine atom, a hydroxyl group, a methyl group, a tert-butyl group, a trifluoromethyl group and a methoxy group,

[0063] -R1' represents a hydrogen atom bonded to the nitrogen atom at the 1- or 3-position of the dihydrotriazine ring,

[0064] - R2 and R3 each represent a methyl group and

[0065] -R4 represents n-octyl, n-nonyl or n-decyl.

[0066] Particularly preferably,

[0067] - R1 represents a benzyl group, which is optionally substituted by 1 to 3 substituents selected from the group consisting of a fluorine atom, a chlorine atom, a hydroxyl group, a methyl group, a tert-butyl group, a trifluoromethyl group and a methoxy group, preferably by 1 to 3 methyl groups, particularly preferably by methyl groups,

[0068] -R1' represents a hydrogen atom bonded to the nitrogen atom at the 1- or 3-position of the dihydrotriazine ring,

[0069] - R2 and R3 each represent a methyl group and

[0070] -R4 represents n-octyl, n-nonyl or n-decyl.

[0071] In another embodiment of the present invention,

[0072] - R1 denotes phenyl, 4-chlorophenyl, 2,4-difluorophenyl, 2,3,4-trifluorophenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 2-methoxy-4-tert-butylphenyl, 4-trifluoromethoxyphenyl, benzyl, methylbenzyl such as in particular 4-methylbenzyl, 4-methoxybenzyl, 3,4-dimethoxybenzyl, 4-hydroxybenzyl, 3,4-dichlorobenzyl, 2,3,4-trichlorobenzyl, 4-trifluoromethylbenzyl, 1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, 2-phenylpropyl or 3-phenylpropyl, preferably methylbenzyl, particularly preferably 4-methylbenzyl,

[0073] -R1' represents a hydrogen atom bonded to the nitrogen atom at the 1- or 3-position of the dihydrotriazine ring,

[0074] - R2 and R3 each represent a methyl group and

[0075] -R4 represents n-octyl, n-nonyl or n-decyl.

[0076] In another embodiment of the present invention, R1 represents methylbenzyl, preferably 4-methylbenzyl, and / or R2 and R3 each represent methyl and / or R4 represents n-octyl. Preferably, R1 represents methylbenzyl, preferably 4-methylbenzyl, R2 and R3 each represent methyl and R4 represents n-octyl.

[0077] In another embodiment of the invention, R1 represents methylbenzyl, preferably 4-methylbenzyl, R1' represents a hydrogen atom bonded to the nitrogen atom in position 1 or 3 of the dihydrotriazine ring, R2 and R3 each represent a methyl group and R4 represents n-octyl.

[0078] Particularly preferably, the dihydrotriazine compound has the following formula Ia:

[0079]

[0080] Alternatively, the dihydrotriazine compound may have the following formula Ib:

[0081]

[0082] In another embodiment of the present invention, the dihydrotriazine compound or its salt is 4-octylamino-1,6-dihydro-6,6-dimethyl-2-(4'-methylbenzylamino)-1,3,5-triazine gluconate, which can also be referred to as 6,6-dimethyl-N 2 -(4-Methylbenzyl)-N 4-octyl-1,6-dihydro-[1,3,5]-triazine-2,4-diamine gluconate, or a tautomer thereof. The dihydrotriazine compound or its salt is preferably 4-octylamino-1,6-dihydro-6,6-dimethyl-2-(4'-methylbenzylamino)-1,3,5-triazine-D-gluconate, which may also be referred to as 6,6-dimethyl-N 2 -(4-Methylbenzyl)-N 4 -octyl-1,6-dihydro-[1,3,5]-triazine-2,4-diamine-D-gluconate, or a tautomer thereof. It has been found that the dihydrotriazine compounds disclosed in this paragraph or the dihydrotriazine compound salts disclosed in this paragraph are particularly effective for preventing or treating mucous membranes and / or wounds and / or infections and / or infectious diseases, especially wounds and / or infections and / or infectious diseases caused or co-caused by fungi (especially yeasts).

[0083] The dihydrotriazine compound mentioned in the preceding paragraph or the dihydrotriazine compound salt mentioned in the preceding paragraph 4-octylamino-1,6-dihydro-6,6-dimethyl-2-(4'-methylbenzylamino)-1,3,5-triazine-D-gluconate is commercially available under the trade name "Femotaxidine" and can be used as the following formula Ia # express:

[0084]

[0085] In another embodiment of the present invention, the dihydrotriazine compound of general formula I or its salt is 4-octylamino-3,6-dihydro-6,6-dimethyl-2-(4'-methylbenzylamino)-1,3,5-triazine gluconate, in particular 4-octylamino-3,6-dihydro-6,6-dimethyl-2-(4'-methylbenzylamino)-1,3,5-triazine-D-gluconate or its tautomer.

[0086] In another embodiment of the invention, the proportion of the dihydrotriazine compound of the general formula I or its tautomer or its salt is 0.001% to 1.00% by weight, in particular 0.01% to 0.50% by weight, preferably 0.025% to 0.25% by weight, based on the total weight of the aqueous composition. It has been found that the proportions of the dihydrotriazine compound or its tautomer or its salt disclosed in this paragraph are particularly advantageous in preventing or treating mucous membranes and / or wounds and / or infections and / or infectious diseases, in particular wounds and / or infections and / or infectious diseases caused or co-caused by fungi, in particular yeasts.

[0087] In another embodiment of the present invention, the defoaming agent is selected from alkylamides, silicones, poloxamers and a combination of at least two of the defoaming agents, in particular a mixture.

[0088] The alkylamide may in particular be an alkylamide of the formula R1-NH-R2, wherein R1 is n-octyl, isooctyl or 2-ethylhexyl, and R2 is n-octane or isooctane, n-nonane or isononane or n-decane or isodecane. According to the invention, the alkylamide may also be a combination of at least two of the corresponding alkylamides, in particular a mixture.

[0089] The silicone may be a polydimethylsiloxane, a polyether silicone (silicone polyethylene glycol or silicone polypropylene glycol) or a 3D-modified silicone, also called a crosslinked silicone, or a combination of at least two of the silicones mentioned, in particular a mixture.

[0090] The poloxamer preferably has 2 to 130 structural units -CH2-CH2-O- and / or 15 to 67 structural units -CHCH3-CH2-O- per molecule.

[0091] In the sense of the present invention, the expression "poloxamers" is understood to mean block copolymers of ethylene oxide and propylene oxide.

[0092] In particular, the poloxamer may be poloxamer 407, poloxamer 188 or a combination, in particular a mixture, thereof.

[0093] In addition, the defoamer can be a combination of alkylamide and siloxane, particularly a mixture. This combination of defoamers is particularly advantageous in suppressing or weakening the foam formation of the dihydrazine compound or its tautomer or its salt. In this case, the ratio of alkylamide, particularly the active ratio, can be 0.0001% by weight to 0.1% by weight, particularly 0.0005% by weight to 0.05% by weight, preferably 0.001% by weight to 0.05% by weight, based on the total weight of the aqueous composition, and the ratio of the siloxane, particularly the active ratio, can be 0.00001% by weight to 0.01% by weight, particularly 0.00002% by weight to 0.005% by weight, preferably 0.00005% by weight to 0.005% by weight, based on the total weight of the aqueous composition.

[0094] In another embodiment of the present invention, the proportion of the defoamer is 0.0001% to 2.0% by weight, in particular 0.0005% to 1.5% by weight, preferably 0.001% to 1.0% by weight, based on the total weight of the aqueous composition. In particular, it has been found that the proportion of the defoamer disclosed in this paragraph is particularly advantageous in inhibiting or reducing foam formation caused by the dihydrotriazine compound of the general formula I or its tautomer or its salt.

[0095] In another embodiment of the present invention, the aqueous composition further comprises a surfactant, in particular a nonionic surfactant and / or a zwitterionic surfactant, with the proviso that the surfactant, in particular a nonionic surfactant and / or a zwitterionic surfactant and the defoamer are selected differently from one another, i.e. the surfactant and the defoamer are different compounds.

[0096] In the sense of the present invention, the expression “nonionic surfactant” means a surfactant which comprises no ionizable functional groups and therefore does not separate into ions in water or aqueous liquids.

[0097] Nonionic or zwitterionic surfactants have the advantage in particular that they have no or little interaction with dihydrotriazine compounds and, moreover, are highly tolerated by mucous membranes and wounds.

[0098] The nonionic surfactant is preferably selected from poloxamers, fatty alcohol alkoxylates such as fatty alcohol ethoxylates, polyvinylpyrrolidone, alkyl polyglucosides and combinations of at least two of the nonionic surfactants, in particular mixtures. It has been found that the nonionic surfactants mentioned in this paragraph and described in more detail below are particularly suitable for reducing or avoiding the unfavorable irritation potential of the dihydrotriazine compounds of the general formula I or their tautomers or salts thereof from the perspective of wound treatment.

[0099] The poloxamer preferably has 2 to 130 structural units -CH2-CH2-O- and / or 15 to 67 structural units -CHCH3-CH2-O- per molecule.

[0100] The poloxamer may in particular be poloxamer 407, poloxamer 188 or a combination thereof, in particular a mixture.

[0101] According to the invention, the use of poloxamers as surfactants may be particularly preferred, since poloxamers, in addition to their surfactant properties, also have antifoaming or defoaming properties and / or emulsifying properties. This makes it particularly advantageous to additionally inhibit, reduce or suppress foam formation caused by dihydrotriazine compounds of the general formula I or their tautomers or their salts and / or to achieve or improve a uniform distribution of the defoamer in the aqueous composition.

[0102] According to the invention, polyvinylpyrrolidone may also be particularly preferred as a surfactant, since the surfactant has, in addition to its surfactant properties, also an emulsifying property. The advantages further mentioned in the previous paragraph apply mutatis mutandis. In addition, the advantage of using polyvinylpyrrolidone is that it can bind water and thus act as a viscosity regulator.

[0103] In the sense of the present invention, the expression "fatty alcohol alkoxylate" is understood to mean a nonionic surfactant whose lipophilic part comprises or consists of a fatty alcohol and whose hydrophilic part comprises or consists of a polyalkylene glycol, in particular a short-chain polyalkylene glycol. The fatty alcohol may in particular be an alcohol derived from caprylic acid, capric acid, lauric acid, palmitic acid, stearic acid or oleic acid or a branched isononyl, isoundecyl, isotridecyl, isopentadecyl or isonadecyl alcohol. In the sense of the present invention, the fatty alcohol alkoxylate may also be referred to as a polyalkylene glycol ether.

[0104] As already mentioned, the fatty alcohol alkoxylates may in particular be fatty alcohol ethoxylates.

[0105] The fatty alcohol ethoxylate is preferably a polyoxyethylene ether of lauryl alcohol, a polyoxyethylene ether of myristyl alcohol, a polyoxyethylene ether of cetyl alcohol, a polyoxyethylene ether of cetearyl alcohol, a polyoxyethylene ether of stearyl alcohol, a polyoxyethylene ether of oleyl alcohol, a polyoxyethylene ether of isononyl alcohol, a polyoxyethylene ether of isoundecanol, a polyoxyethylene ether of isotridecanol, a polyoxyethylene ether of isopentadecyl alcohol, a polyoxyethylene ether of isoheptadecanol, a polyoxyethylene ether of isonadecanol or a combination of at least two of the polyoxyethylene ethers mentioned, in particular a mixture.

[0106] The fatty alcohol ethoxylate can in particular be selected from the group consisting of polyoxyethylene (4) lauryl ether, polyoxyethylene (7) lauryl ether, polyoxyethylene (9) lauryl ether, polyoxyethylene (23) lauryl ether, polyoxyethylene (2) cetyl ether, polyoxyethylene (10) cetyl ether, polyoxyethylene (20) cetyl ether, polyoxyethylene (6) cetearyl ether, polyoxyethylene (20) cetearyl ether, polyoxyethylene (25) cetearyl ether, polyoxyethylene (2) stearyl ether, polyoxyethylene (10) stearyl ether, polyoxyethylene (20) stearyl ether, polyoxyethylene (2) oleyl ether, polyoxyethylene (10) oleyl ether, polyoxyethylene (20) oleyl ether, polyoxyethylene (10) monodecyl ether, polyoxyethylene (10) tridecyl ether and a combination, in particular a mixture, of at least two of the fatty alcohol ethoxylates mentioned.

[0107] In other words, the alcohol ethoxylate can in particular be chosen from: Laureth-4, Laureth-7, Laureth-9, Laureth-23, Ceteth-2, Ceteth-10, Ceteth-20, Ceteareth-6, Ceteareth-20, Ceteareth-25, Steareth-2, Steareth-10, Steareth-20, Oleth-2, Oleth-10, Oleth-20, Deceth-10, Trideceth-10 and a combination, in particular a mixture, of at least two of the alcohol ethoxylates mentioned.

[0108] Fatty alcohol alkoxylates, in particular fatty alcohol ethoxylates, have the advantage that they not only have surfactant properties but also additionally have an emulsifying effect.

[0109] In the sense of the present invention, the expression "alkyl polyglucosides" is understood to mean nonionic sugar surfactants having or consisting of one or more glucose units and an alkyl group, in particular a long-chain alkyl group. The one or more glucose units serve as hydrophilic components, while the alkyl group is a hydrophobic group.

[0110] The alkyl polyglucoside preferably has 1 to 5 glucose units and / or an alkyl group having 6 to 20 carbon atoms, in particular 6 to 16 carbon atoms, preferably 8 to 14 carbon atoms.

[0111] The alkyl polyglucoside is preferably C8- to C 20 -alkyl polyglucose, especially C8- to C 16 -Alkyl polyglucose.

[0112] The alkyl polyglucosides are particularly preferably lauryl polyglucose, decyl polyglucose, coconut oil polyglucose or a mixture of at least two of the alkyl polyglucosides mentioned. Here, the alkyl group of decyl polyglucose preferably has 8 to 16 carbon atoms, in particular 10 carbon atoms. The alkyl group of lauryl polyglucose preferably has 12 to 16 carbon atoms, in particular 12 carbon atoms. The alkyl group of coconut oil polyglucose preferably has 8 to 16 carbon atoms.

[0113] Alkyl polyglucosides also have the advantage that they not only have surfactant properties but are also compounds that have an emulsifying effect.

[0114] In another embodiment of the present invention, the surfactant is a zwitterionic surfactant.

[0115] In the sense of the present invention, the expression “zwitterionic surfactants” means surfactants which have negatively and positively charged functional groups (so-called amphoteric surfactants).

[0116] The zwitterionic surfactant is preferably an alkylamidoalkylbetaine, especially alkylamidoethylbetaine, alkylamidopropylbetaine or a combination thereof, especially a mixture.

[0117] The alkylamidoalkylbetaine is particularly preferably an alkylamidoalkylbetaine of a fatty acid. Here, the fatty acid preferably has 8 to 18 carbon atoms. The fatty acid can be a saturated or unsaturated fatty acid. The fatty acid is preferably caprylic acid, capric acid, undecylenic acid (undecyl-10-enoic acid), undecanoic acid (n-undecanoic acid), lauric acid, stearic acid, ricinoleic acid or coconut fatty acid.

[0118] The alkylamidoalkylbetaine is preferably selected from the group consisting of octylamidoalkylbetaine, caprylamidoalkylbetaine, undecylenamidoalkylbetaine, undecylamidoalkylbetaine, laurylamidoalkylbetaine, lauryldimethylaminoacetic acid betaine, stearamidoalkylbetaine, ricinoleamidoalkylbetaine, cocoamidoalkylbetaine and a combination of at least two of the mentioned alkylamidoalkylbetaines, in particular a mixture.

[0119] The alkylamidoethyl betaine is preferably an alkylamidoethyl betaine based on a fatty acid, in particular a fatty acid having 8 to 18 carbon atoms. The fatty acid may be a saturated or unsaturated fatty acid. The fatty acid is preferably caprylic acid, capric acid, undecylenic acid (undec-10-enoic acid), undecanoic acid (n-undecanoic acid), lauric acid, stearic acid, ricinoleic acid or coconut fatty acid.

[0120] The alkylamidoethyl betaine is particularly preferably selected from the group consisting of octylamidoethyl betaine, caprylamidoethyl betaine, undecylenamidoethyl betaine, undecylamidoethyl betaine, lauramidoethyl betaine, cocoamidoethyl betaine, stearamidoethyl betaine, ricinoleamidoethyl betaine and a combination of at least two of the alkylamidoethyl betaines mentioned, in particular a mixture.

[0121] The alkylamidopropyl betaine is preferably an alkylamidopropyl betaine based on a fatty acid, in particular a fatty acid having 8 to 18 carbon atoms. The fatty acid may be a saturated or unsaturated fatty acid. The fatty acid is preferably caprylic acid, capric acid, undecylenic acid (undec-10-enoic acid), undecanoic acid (n-undecanoic acid), lauric acid, stearic acid, ricinoleic acid or coconut fatty acid.

[0122] The alkylamidopropyl betaine is particularly preferably selected from octylamidopropyl betaine, caprylamidopropyl betaine, undecylenamidopropyl betaine, undecylamidopropyl betaine, cocoamidopropyl betaine, stearamidopropyl betaine, ricinoleamidopropyl betaine and a combination of at least two of the mentioned alkylamidopropyl betaines, in particular a mixture.

[0123] The optionally provided surfactant may furthermore be a combination, in particular a mixture, of the surfactants described in the preceding paragraphs, in particular a combination, in particular a mixture, of a nonionic surfactant and a zwitterionic surfactant. In this respect, reference is made fully to the surfactants described in the preceding paragraphs.

[0124] Furthermore, the surfactant may be a poloxamer, wherein the aqueous composition has no defoaming compounds and / or no emulsifying compounds in addition to the surfactant. Due to the already mentioned defoaming and / or emulsifying properties of the poloxamer, the additional use of defoamers and / or emulsifiers may be particularly advantageously not required. With regard to further features and advantages of the poloxamer, reference is made entirely to the previous description.

[0125] In addition, the surfactant may be polyvinylpyrrolidone, wherein the aqueous composition has no defoaming compound and / or no emulsifying compound and / or no water-binding compound except the surfactant. Due to the defoaming and / or emulsifying and / or thickening (i.e. water-binding) properties of the polyvinylpyrrolidone already mentioned, it is particularly advantageous that no additional defoaming agent and / or emulsifying agent and / or thickening agent is required. Regarding other features and advantages of polyvinylpyrrolidone, reference is made to the previous description in full.

[0126] Furthermore, the surfactant may be a fatty alcohol alkoxylate, in particular a fatty alcohol ethoxylate, and / or an alkyl polyglucoside, wherein the aqueous composition contains no emulsifying compounds other than the surfactant. Due to the already mentioned emulsifying properties of the fatty alcohol alkoxylate, in particular a fatty alcohol ethoxylate and / or an alkyl polyglucoside, it may be particularly advantageously not necessary to additionally use an emulsifier. With regard to further features and advantages of the fatty alcohol alkoxylate, in particular a fatty alcohol ethoxylate, and / or an alkyl polyglucoside, reference is made fully to the previous description.

[0127] In another embodiment of the invention, the proportion of surfactant, in particular the active proportion, is 0.01% to 10.0% by weight, in particular 0.05% to 2.0% by weight, preferably 0.1% to 1.0% by weight, based on the total weight of the aqueous composition. In particular, the surfactant proportions disclosed in this paragraph are particularly suitable for significantly reducing the irritation effect of the dihydrotriazine compound of the general formula I or its tautomer or its salt.

[0128] In another embodiment of the invention, the aqueous composition further comprises an emulsifier, provided that the emulsifier and the optionally present surfactant are selected differently from each other, i.e. the emulsifier and the surfactant are different compounds. The emulsifier is preferably selected from alcohol ethoxylates, alkyl polyglucosides, polysorbates, ethoxylated castor oil and a combination of at least two of the mentioned emulsifiers, in particular a mixture. With regard to further features and advantages of the surfactant, reference is made entirely to the previous description.

[0129] The alcohol ethoxylate is preferably a fatty alcohol ethoxylate.

[0130] The fatty alcohol ethoxylate can be, in particular, a polyoxyethylene ether of lauryl alcohol, a polyoxyethylene ether of myristyl alcohol, a polyoxyethylene ether of isononyl alcohol, a polyoxyethylene ether of isoundecanol, a polyoxyethylene ether of isotridecanol, a polyoxyethylene ether of cetyl alcohol, a polyoxyethylene ether of cetearyl alcohol, a polyoxyethylene ether of stearyl alcohol, a polyoxyethylene ether of oleyl alcohol or a combination of at least two of the polyoxyethylene ethers mentioned, in particular a mixture.

[0131] The alcohol ethoxylate is preferably selected from polyoxyethylene (4) lauryl ether, polyoxyethylene (7) lauryl ether, polyoxyethylene (9) lauryl ether, polyoxyethylene (23) lauryl ether, polyoxyethylene (2) cetyl ether, polyoxyethylene (10) cetyl ether, polyoxyethylene (20) cetyl ether, polyoxyethylene (6) cetearyl ether, polyoxyethylene (20) cetearyl ether, polyoxyethylene (25) cetearyl ether, polyoxyethylene (2) stearyl ether, polyoxyethylene (10) stearyl ether, polyoxyethylene (20) stearyl ether, polyoxyethylene (2) oleyl ether, polyoxyethylene (10) oleyl ether, polyoxyethylene (20) oleyl ether, polyoxyethylene (10) monodecyl ether, polyoxyethylene (10) tridecyl ether and a combination, in particular a mixture, of at least two of the fatty alcohol ethoxylates mentioned.

[0132] In other words, the alcohol ethoxylate may preferably be selected from Laureth-4, Laureth-7, Laureth-9, Laureth-23, Ceteth-2, Ceteth-10, Ceteth-20, Ceteareth-6, Ceteareth-20, Ceteareth-25, Steareth-2, Steareth-10, Steareth-20, Oleth-2, Oleth-10, Oleth-20, Deceth-10, Trideceth-10 and a combination, in particular a mixture, of at least two of the alcohol ethoxylates mentioned.

[0133] The alkyl polyglucoside preferably has 1 to 5 glucose units and / or an alkyl group having 8 to 20 carbon atoms, in particular 8 to 16 carbon atoms, preferably 8 to 14 carbon atoms.

[0134] The alkyl polyglucoside is preferably C8- to C 20 -alkyl polyglucose, especially C8- to C 16 -Alkyl polyglucose.

[0135] The alkyl polyglucosides are particularly preferably lauryl polyglucose, decyl polyglucose, coconut oil polyglucose or a mixture of at least two of the alkyl polyglucosides mentioned. Here, the alkyl group of decyl polyglucose preferably has 8 to 16 carbon atoms, in particular 10 carbon atoms. The alkyl group of lauryl polyglucose preferably has 12 to 16 carbon atoms, in particular 12 carbon atoms. The alkyl group of coconut oil polyglucose preferably has 8 to 16 carbon atoms.

[0136] In the sense of the present invention, the expression "polysorbate" is understood to mean ethoxylated sorbitan fatty acid esters.

[0137] The polysorbate can in particular be selected from the group consisting of: polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (4) sorbitan monolaurate, polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (4) sorbitan monostearate, polyoxyethylene (20) sorbitan tristearate, polyoxyethylene (20) sorbitan monooleate, polyoxyethylene (5) sorbitan monooleate, polyoxyethylene (20) sorbitan trioleate, polyoxyethylene (20) sorbitan monoisostearate and combinations of at least two of the polysorbates mentioned, in particular mixtures.

[0138] In other words, the polysorbate can in particular be selected from the group consisting of: polysorbate 20, polysorbate 21, polysorbate 40, polysorbate 60, polysorbate 61, polysorbate 65, polysorbate 80, polysorbate 81, polysorbate 85, polysorbate 120 and a combination, in particular a mixture, of at least two of the polysorbates mentioned.

[0139] In another embodiment of the invention, the proportion of the emulsifier is 0.001% to 1.5% by weight, in particular 0.01% to 1.5% by weight, in particular 0.02% to 1.0% by weight, preferably 0.05% to 0.5% by weight, based on the total weight of the aqueous composition. In particular, it has been found that the emulsifier proportions disclosed in this paragraph are particularly advantageous with regard to a uniform distribution of the defoamer in the aqueous composition.

[0140] In another embodiment of the present invention, the aqueous composition further has an additive selected from the group consisting of complexing agents, wetting agents, acids, bases, organic solvents and combinations of at least two of the mentioned additives, in particular mixtures.

[0141] The complexing agent can in particular be selected from: citric acid, tartaric acid, succinic acid, methylglycine diacetate, ethylenediaminetetraacetate, N,N'-bis(carboxymethyl)-L-glutamate, polyaspartic acid, iminodisuccinate, salts of the complexing agents mentioned and combinations of at least two of the complexing agents mentioned, in particular mixtures.

[0142] Furthermore, the proportion of complexing agents can be 0.01% to 10.0% by weight, in particular 0.02% to 2.0% by weight, preferably 0.05% to 1.0% by weight, based on the total weight of the aqueous composition.

[0143] The humectant can be selected from glycerol, polydextrose, sorbitol, ethylene glycol, polyethylene glycol, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, caprylyl glycol, glucose, fructose, glucuronic acid, lactose, lactic acid, lactate, lactulose, sucrose, hyaluronic acid, xylitol, xylose and a combination of at least two of the mentioned humectants, in particular a mixture.

[0144] Furthermore, the proportion of wetting agents can be 0.05% to 10.0% by weight, in particular 0.1% to 7.5% by weight, preferably 0.5% to 5% by weight, based on the total weight of the aqueous composition.

[0145] The acid can be selected from formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutaric acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, ascorbic acid, aspartic acid, glutamic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid and a combination of at least two of the acids mentioned, in particular a mixture.

[0146] Furthermore, the proportion of the acid can be 0.01% to 10.0% by weight, in particular 0.1% to 6.0% by weight, preferably 0.1% to 5.0% by weight, based on the total weight of the aqueous composition.

[0147] The base may be chosen from sodium hydroxide, potassium hydroxide, calcium hydroxide and magnesium hydroxide, and combinations, in particular mixtures, of at least two of the bases mentioned.

[0148] Furthermore, the proportion of the base can be 0.01% to 10.0% by weight, in particular 0.1% to 6.0% by weight, preferably 0.1% to 5.0% by weight, based on the total weight of the aqueous composition.

[0149] The organic solvent may be selected from ethanol, 1-propanol, -2-propanol and a combination of at least two of the mentioned organic solvents, in particular a mixture.

[0150] Furthermore, the proportion of organic solvents can be 0.1% to 10.0% by weight, in particular 0.5% to 10.0% by weight, preferably 1.0% to 10.0% by weight, based on the total weight of the aqueous composition.

[0151] The aqueous composition preferably has a proportion of water of >80% by weight, in particular >90% by weight, based on the total weight of the aqueous composition.

[0152] In another embodiment of the present invention, the aqueous composition is an aqueous composition for use in the prevention or treatment of mucous membranes and / or wounds, in particular acute or chronic wounds, and / or for use in the prevention or treatment of infections, in particular infections caused or co-caused by fungi (in particular yeasts), and / or for use in the prevention or treatment of infectious diseases, in particular infectious diseases caused or co-caused by fungi (in particular yeasts). The infectious disease may be, for example, candidiasis or erysipelas.

[0153] From the following description of preferred embodiments, other features and advantages of the present invention are obtained. Here, each feature can be realized individually or in combination with each other in each case. The described embodiments are only used to further illustrate the present invention, but the present invention is not limited thereto.

[0154] Examples

[0155] 1. Preparation of wound washing solution according to the present invention

[0156] 9912.5 g of water were pre-added to a suitable mixing reactor. The agitator was then adjusted so that a slight ring formed on the surface of the water. Subsequently, 25.00 g of Tween 20 (polysorbate 20) and 2.50 g of N-(2-ethylhexyl) isononamide were added. 50.00 g of cocamidopropyl betaine (50%) was then added. 10.00 g of femotaxidine was then added. Subsequently, the mixture was stirred for 1 hour. The solution obtained here had the composition given in Table 1 below:

[0157] Femotaxidine 0.100% by weight Purify water 99.125% by weight Cocamidopropyl Betaine (50%) 0.500% by weight Tween20 0.250 wt% Alkyl amide 0.025 wt%

[0158] Table 1: Examples of wound irrigation solutions according to the present invention.

[0159] 2. Preparation of another wound washing solution according to the present invention

[0160] 9889.0 g of water were added in advance to a suitable mixing reactor. The agitator was then adjusted so that a slight ring formed on the surface of the water. Subsequently, 40.00 g of Tween 20 and 1.00 g of polyether siloxane were added. Then 50.00 g of cocamidopropyl betaine (50%) was added. Finally, 20.00 g of femotaxidine was added. Subsequently, the mixture was stirred for 1 hour. The solution obtained here had the composition given in Table 2 below:

[0161] Femotaxidine 0.200 wt% Purify water 98.890% by weight Cocamidopropyl Betaine (50%) 0.500% by weight Tween20 0.400 wt% Siloxane 0.010 wt%

[0162] Table 2: Examples of wound irrigation solutions according to the present invention.

[0163] 3. Preparation of another wound washing solution according to the present invention

[0164] 9885.0 g of water were added in advance to a suitable mixing reactor. The agitator was then adjusted so that a slight ring formed on the surface of the water. Subsequently, 17.50 g of Laureth-7 and 2.50 g of N-(2-ethylhexyl)isononanamide were added. Then 90.00 g of undecylenamidopropyl betaine (35%) was added. Finally, 5.00 g of Femotaxidine was added. Subsequently, the mixture was stirred for 1 hour. The solution obtained here had the composition given in Table 3 below:

[0165] Femotaxidine 0.050 wt% Purify water 98.850% by weight Undecylenamidopropyl betaine (35%) 0.900% by weight Laureth-7 0.175 wt% Alkyl amide 0.025 wt%

[0166] Table 3: Another example of a wound irrigation solution according to the present invention.

[0167] 4. Preparation of another wound washing solution according to the present invention

[0168] 9833.0 g of water were added in advance to a suitable mixing reactor. The agitator was then adjusted so that a slight ring formed on the surface of the water. Subsequently, 15.00 g of laureth-7 and 2.00 g of polyether siloxane were added. Then 125.0 g of undecylenamidopropyl betaine (35%) was added. Finally, 25.00 g of femotaxidine was added. Subsequently, the mixture was stirred for 1 hour. The solution obtained here had the composition given in the following Table 4:

[0169] Femotaxidine 0.250 wt% Purify water 98.330% by weight Undecylenamidopropyl betaine (35%) 1.250 wt% Laureth-7 0.150% by weight Siloxane 0.020 wt%

[0170] Table 4: Another example of a wound irrigation solution according to the present invention.

[0171] 5. Preparation of another wound washing solution according to the present invention

[0172] 9904.4 g of water were pre-charged in a suitable mixing reactor. The agitator was then adjusted so that a slight ring formed on the surface of the water. Subsequently, 15.00 g of Laureth-7, 0.50 g of N-(2-ethylhexyl)isononamide and 0.10 g of 3D-modified "crosslinked" siloxane were added. Then 70.00 g of Octylamidopropyl Betaine (35%) were added. Finally, 10.00 g of Femotaxidine were added. Subsequently, the mixture was stirred for 1 hour. The solution obtained here had the composition given in the following Table 5:

[0173] Femotaxidine 0.100% by weight Purify water 99.044% by weight Alkylamidopropyl betaine (35%) 0.700 wt% Laureth-7 0.150% by weight Alkyl amide 0.005 wt% Siloxane 0.001 wt%

[0174] Table 5: Another example of a wound washing solution according to the present invention.

[0175] 6. Preparation of another wound washing solution according to the present invention

[0176] 9889.5 g of water were pre-charged in a suitable mixing reactor. The agitator was then adjusted so that a slight ring formed on the surface of the water. Subsequently, 20.00 g of Poloxamer 188 and 0.50 g of 3D-modified "cross-linked" siloxane were added. Then 50.00 g of cocamidopropyl betaine (50%) was added. Finally, 10.00 g of femotaxidine was added. Subsequently, the mixture was stirred for 1 hour. The solution obtained here had the composition given in Table 6 below:

[0177] Femotaxidine 0.100% by weight Purify water 98.895% by weight Cocamidopropyl Betaine (50%) 0.800 wt% Poloxamer 0.200 wt% Siloxane 0.005 wt%

[0178] Table 6: Another example of a wound irrigation solution according to the present invention.

[0179] 7. Preparation of another wound washing solution according to the present invention

[0180] 9958.0 g of water were added in advance to a suitable mixing reactor. The agitator was then adjusted so that a slight ring was formed on the surface of the water. Subsequently, 30.00 g of Tween 20 and 2.00 g of N-(2-ethylhexyl)isononylamide were added. 10.00 g of Femotaxidine was then added. Subsequently, the mixture was stirred for 1 hour. The solution obtained here has the composition given in the following Table 7:

[0181] Femotaxidine 0.100% by weight Purify water 99.580% by weight Tween20 0.300 wt% Alkyl amide 0.020 wt%

[0182] Table 7: Another example of a wound irrigation solution according to the present invention.

[0183] 8. Preparation of another wound washing solution according to the present invention

[0184] 9966.4 g of water were pre-charged in a suitable mixing reactor. The agitator was then adjusted so that a slight ring formed on the surface of the water. Subsequently, 12.50 g of Laureth-7, 1.00 g of N-(2-ethylhexyl)isononamide and 0.10 g of 3D-modified "crosslinked" siloxane were added. 20.00 g of Femotaxidine were then added. Subsequently, the mixture was stirred for 1 hour. The solution obtained here had the composition given in Table 8 below:

[0185] Femotaxidine 0.200 wt% Purify water 99.664% by weight Laureth-7 0.125 wt% Alkyl amide 0.010 wt% Siloxane 0.001 wt%

[0186] Table 8: Another example of a wound irrigation solution according to the present invention.

[0187] 9. Preparation of another wound washing solution according to the present invention

[0188] 9820.0 g of water were added in advance to a suitable mixing reactor. The agitator was then adjusted so that a slight ring formed on the surface of the water. Subsequently, 500.00 g of polyvinylpyrrolidone were added. Then 70.00 g of undecylenamidopropyl betaine (35%) were added. Then 10.00 g of femotaxidine were added. Subsequently, the mixture was stirred for 1 hour. The solution obtained here had the composition given in the following Table 9:

[0189] Femotaxidine 0.100% by weight Purify water 98.200% by weight Polyvinylpyrrolidone 5.000 wt% Undecylenamidopropyl betaine (35%) 0.700 wt%

[0190] Table 9: Another example of a wound irrigation solution according to the present invention.

[0191] 10. Preparation of another wound washing solution according to the present invention

[0192] 9890.0 g of water were added in advance to a suitable mixing reactor. The agitator was then adjusted so that a slight ring formed on the surface of the water. Subsequently, 100.00 g of Poloxamer 188 were added. Then 10.00 g of Femotaxidine were added. Subsequently, the mixture was stirred for 1 hour. The solution obtained here had the composition given in the following Table 10:

[0193] Femotaxidine 0.100% by weight Purify water 98.900% by weight Poloxamer 1.000 wt%

[0194] Table 10: Another example of a wound irrigation solution according to the present invention.

[0195] 11. Preparation of wound irrigation solution not according to the present invention

[0196] 9980.0 g of water were added in advance to a suitable mixing reactor. The agitator was then adjusted so that a slight ring formed on the surface of the water. Subsequently, 20.00 g of Femotaxidine were added. Subsequently, the mixture was stirred for 1 hour. The solution obtained here had the composition given in the following Table 11:

[0197]

[0198]

[0199] Table 11: Examples of wound irrigation solutions not according to the invention.

[0200] The wound wash solutions according to the invention prepared at 1 to 10 have a large difference in foaming behavior relative to the aqueous femotaxidine solution (0.1 wt. % or 0.2 wt. % [solution 11]). In the case of the wound wash solutions according to the invention, the foam requires much more energy to form and then collapses within a very short time, in particular within a few minutes, whereas in the case of the aqueous femotaxidine solution used for comparison purposes, the foam forms very easily and remains for a period of more than 10 hours. In particular, formulations 5 and 8 show very rapid foam collapse.

[0201] Compared to the commercial formulation Octenisept, formulations 9 and 11 showed a significantly faster effect on yeasts according to EN 13624 and were also convincing in the HET-CAM test with significantly lower irritation.

[0202]

[0203] Log 10 Gives a reduction in microbial count; the criterion for passing the test according to EN 13624 is >4.

[0204] The HET-CAM (Chicken Embryo Chorioallantoic Membrane Test) is a method for testing the mucosal tolerance of chemical substances. The CAM is the choroid of the egg. To perform the test, the substance to be tested is placed on the CAM. The reaction of the membrane (bleeding, changes in blood vessels or egg white) is observed, compared to a reference substance (e.g. sodium dodecyl sulfate) and evaluated. This test is considered the official preliminary test for testing mucosal tolerance.

[0205] In HET-CAM, 6 indicates moderate irritation, while values ​​of 1-5 are rated as low irritation.

Claims

1. An aqueous composition having - A dihydrotriazine compound of the following general formula I or its tautomer or its salt: in - R1 represents (i) phenyl or phenylalkyl, wherein the phenylalkyl is benzyl, methylbenzyl, 1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, 2-phenylpropyl or 3-phenylpropyl, -R1' represents a hydrogen atom bonded to the nitrogen atom at the 1- or 3-position of the dihydrotriazine ring, - R2 and R3 independently represent a hydrogen atom or a methyl group, - R4 represents an alkyl group having 7 to 16 carbon atoms, and - the dotted line indicates that the position of the double bond is between the 1 and 2 positions or between the 2 and 3 positions of the dihydrotriazine ring, and - a defoaming agent, wherein the defoaming agent is selected from the group consisting of alkylamides, siloxanes, poloxamers and a combination of at least two of the defoaming agents, in, The proportion of the dihydrotriazine compound is 0.001 to 1.00% by weight, based on the total weight of the aqueous composition, and the proportion of the defoaming agent is 0.0001 to 2.0% by weight, based on the total weight of the aqueous composition.

2. The aqueous composition according to claim 1, characterized in that R1 represents a phenyl group or a phenylalkyl group, R1' represents a hydrogen atom bonded to a nitrogen atom at the 1- or 3-position of the dihydrotriazine ring, R2 and R3 each represent a methyl group and R4 represents an n-octyl group, an n-nonyl group or an n-decyl group.

3. The aqueous composition according to claim 1 or 2, characterized in that R1 represents phenyl, benzyl, methylbenzyl, 1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, 2-phenylpropyl or 3-phenylpropyl, R1' represents a hydrogen atom bonded to the nitrogen atom at the 1- or 3-position of the dihydrotriazine ring, R2 and R3 each represent a methyl group and R4 represents an n-octyl group, an n-nonyl group or an n-decyl group.

4. The aqueous composition according to claim 3, wherein R1 represents 4-methylbenzyl.

5. The aqueous composition according to claim 1 or 2, characterized in that R1 represents a methylbenzyl group, and R2 and R3 each represent a methyl group and R4 represents an n-octyl group.

6. The aqueous composition according to claim 5, wherein R1 represents 4-methylbenzyl.

7. The aqueous composition according to claim 1 or 2, characterized in that R1 represents a methylbenzyl group, R1' represents a hydrogen atom bonded to a nitrogen atom at the 1- or 3-position of the dihydrotriazine ring, R2 and R3 each represent a methyl group and R4 represents an n-octyl group.

8. The aqueous composition according to claim 7, wherein R1 represents 4-methylbenzyl.

9. The aqueous composition according to claim 1 or 2, characterized in that The dihydrotriazine compound is 4-octylamino-1,6-dihydro-6,6-dimethyl-2-(4'-methylbenzylamino)-1,3,5-triazine gluconate, 4-octylamino-3,6-dihydro-6,6-dimethyl-2-(4'-methylbenzylamino)-1,3,5-triazine gluconate or its tautomer.

10. The aqueous composition according to claim 1 or 2, characterized in that The proportion of the dihydrotriazine compound is 0.01% to 0.50% by weight, based on the total weight of the aqueous composition. 11 . The aqueous composition according to claim 10 , wherein the proportion of the dihydrotriazine compound is 0.025% by weight to 0.25% by weight, based on the total weight of the aqueous composition.

12. The aqueous composition according to claim 1 or 2, characterized in that The proportion of the defoamer is 0.0005% to 1.5% by weight, based on the total weight of the aqueous composition.

13. The aqueous composition according to claim 12, wherein the proportion of the defoaming agent is 0.001% by weight to 1.0% by weight, based on the total weight of the aqueous composition.

14. The aqueous composition according to claim 1 or 2, characterized in that The aqueous composition further comprises a surfactant, with the proviso that the defoamer and the surfactant are selected differently from each other.

15. The aqueous composition of claim 14, wherein the surfactant is a nonionic surfactant.

16. The aqueous composition according to claim 15, wherein the nonionic surfactant is selected from the group consisting of poloxamers, fatty alcohol alkoxylates, polyvinyl pyrrolidone, alkyl polyglucosides and a combination of at least two of the nonionic surfactants.

17. The aqueous composition according to claim 16, wherein the fatty alcohol alkoxylate is a fatty alcohol ethoxylate.

18. The aqueous composition according to claim 14, characterized in that The surfactant is a zwitterionic surfactant.

19. The aqueous composition of claim 18, wherein the zwitterionic surfactant is an alkylamidoalkylbetaine.

20. The aqueous composition of claim 19, wherein the alkylamidoalkyl betaine is alkylamidoethyl betaine, alkylamidopropyl betaine, or a combination thereof.

21. The aqueous composition according to claim 1 or 2, characterized in that The aqueous composition also has an emulsifier, with the proviso that the emulsifier and the optionally present surfactant are selected differently from one another.

22. The aqueous composition of claim 21, wherein the emulsifier is selected from the group consisting of alcohol ethoxylates, alkyl polyglucosides, polysorbates, ethoxylated castor oil and a combination of at least two of the emulsifiers.

23. The aqueous composition according to claim 21, characterized in that The active proportion of the surfactant is 0.01 to 10.0% by weight, based on the total weight of the aqueous composition, and / or the proportion of the emulsifier is 0.001 to 1.5% by weight, based on the total weight of the aqueous composition.

24. The aqueous composition according to claim 23, wherein the active proportion of the surfactant is 0.05 wt% to 2.0 wt% based on the total weight of the aqueous composition.

25. The aqueous composition according to claim 23, wherein the active proportion of the surfactant is 0.1 wt% to 1.0 wt% based on the total weight of the aqueous composition.

26. The aqueous composition according to claim 23, wherein the proportion of the emulsifier is 0.02% to 1.0% by weight, based on the total weight of the aqueous composition.

27. The aqueous composition according to claim 23, wherein the proportion of the emulsifier is 0.05% to 0.5% by weight, based on the total weight of the aqueous composition.

28. The aqueous composition according to claim 1 or 2, characterized in that The aqueous composition further has an additive selected from the group consisting of a thickener, a complexing agent, a wetting agent, an acid, a base, an organic solvent, and a combination of at least two of the additives.

29. Use of the aqueous composition according to any one of claims 1 to 28 in the preparation of a medicament for preventing or treating infectious diseases caused or co-caused by fungi.

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