DISINFECTANT CONCENTRATES CONTAINING CARBOXYLIC ACIDS AND SHORT-CHAIN ​​AMINO ACIDS

Abstract

The invention relates to disinfectant concentrates containing water, at least one carboxylic acid, and at least one amino acid. The disinfectant concentrates are used, after dilution with water, as disinfectant compositions for surface disinfection, particularly hard surfaces such as floors.

Description

[0001] The invention relates to disinfectant concentrates containing water, at least one carboxylic acid, and at least one amino acid. The disinfectant concentrates can be used, after dilution with water, as disinfectant compositions for surface disinfection, particularly hard surfaces such as floors. State of the art

[0002] Surface disinfectants make an important contribution to infection control. The areas of application for surface disinfectants in healthcare facilities are often classified according to the risk potential of the surfaces to be disinfected. While particularly effective disinfectant compositions with additional sporicidal activity, for example, based on peroxide compounds such as hydrogen peroxide or peracetic acid, are used in high-risk areas, disinfectant compositions containing quaternary ammonium compounds are very frequently used in areas with a lower risk of infection transmission – also for prophylactic disinfection. These products are generally effective against bacteria, fungi, and viruses.

[0003] In its guideline "Hygienic Requirements for the Cleaning and Disinfection of Surfaces," published in the Federal Health Gazette 2022, the Robert Koch Institute (RKI) points out a number of toxicological disadvantages of quaternary ammonium compounds. Furthermore, the use of quaternary ammonium compounds in surface disinfectants leads to the development of resistance in bacteria. At the cellular level, the underlying mechanism is increased efflux pump activity. This is also considered a reason for the development of certain antibiotic resistances. A link between the use of quaternary ammonium compounds and antibiotic resistance has been proven.

[0004] Quaternary ammonium compounds used as active ingredients in surface disinfection are characterized by a surfactant structure, i.e. at least one charged hydrophilic head and one or more long-chain hydrophobic residues.

[0005] Examples are N-alkyl-N-benzyl-N,N-dimethylammonium salts, e.g. the chlorides with C8 to C18 alkyl (CAS 63449-41-2) or C12 to C16 alkyl (CAS 68391-01-5); dialkyldimethylammonium salts, e.g. the chlorides with C8 / C10 alkyl (CAS 68424-95-3) or with C10 / C10 alkyl (CAS 7173-51-5); propionates such as N,N-didecyl-N-methylpoly(oxyethylene)ammonium propionate (CAS 94667-33-1). Further active ingredients that are not or less suitable for the invention are: polyhexamethylene biguanide hydrochloride polymer (PHMB, CAS 32289-58-0), alkylamidopropyl dimmonium chlorides, such as tris(N-C5-17-alkylamidopropyl-N,N-dimethyl-N-(2-hydroxypropyl)ammonio)phosphate trichloride (CAS 83682-78-4, cocoamidopropyl PG dimmonium chloride) or poly-L-lysine (CAS 25104-18-1).

[0006] Since disinfectants are used in large quantities, including for prophylactic surface disinfection, they are predominantly transported or provided as concentrates, which are then diluted on-site by staff. This eliminates the need to transport the water component of the dilutions used. This saves transportation costs and is therefore more environmentally friendly.

[0007] Carboxylic acids are other well-known disinfectant active ingredients. Examples of carboxylic acids used as disinfectant active ingredients include acetic acid, citric acid, salicylic acid, and propionic acid. Lactic acid, glycolic acid, benzoic acid, and tartaric acid are other carboxylic acids that may also be used.

[0008] Many attempts to increase the effectiveness of carboxylic acids are documented in the patent literature in order to reduce the amount of carboxylic acids relative to a required or desired effectiveness.

[0009] For example, DE 102015113641 A1 proposes to utilize a synergistic effect based on the interaction of several carboxylic acids. DE 3229097 C2 mentions acids such as benzoic acid and tartaric acid in combination with alkyl sulfonates, alkyl sulfates, and alcohols.

[0010] In a number of examples for contact lens disinfection, a combination of carboxylic acids and quaternary ammonium compounds is proposed as a component of contact lens storage agents; see, for example, DE 602004008651 T2, WO 2009096038 A1, and EP 2932985 A1. The compositions are adjusted to pH values ​​in the weakly acidic / neutral range. WO 2021156297 A1 discloses a combination of quaternary ammonium compounds with surfactant properties with carboxylic acids for laundry disinfection. US 2023146954 A1 discloses a combination of surfactant active ingredients with hydrogen peroxide and carboxylic acids. However, this combination is not a concentrate that requires dilution, but rather a ready-to-use application.

[0011] Amino acids have also been mentioned in combination with carboxylic acids in isolated cases. EP 2781158 B1, for example, discloses such a combination relating to cleaning and care products for farm animals. Glutamic acid, aspartic acid, and tyrosine are mentioned in one example, but for various reasons, these are not suitable for compositions according to the present invention.

[0012] In EP 3082433 B1, N-acylated amino acids are used as surfactants in combination with carboxylic acids. Arginine and lysine are also used as organic bases. These amino acids substituted with additional basic functional groups are not suitable for the present invention.

[0013] EP 3102661 B1 describes alcoholic solutions with at least 30% alcohol, which may also contain amino acids. In addition, and independently of the presence of amino acids, carboxylic acids may also be present. The mixtures are used undiluted.

[0014] Another antimicrobial ready-to-use product used as a foam spray is disclosed in JP 2019182854 A. In addition to at least 20% ethanol, carboxylic acids and amino acids are also mentioned. The pH of the formulations is around the neutral pH range. CN 113812419 A describes a disinfectant, albeit in solid tablet form, based on chlorine dioxide, which may contain carboxylic acids and the amino acid leucine as an anti-caking agent. Object of the invention

[0015] The objective of the invention was to produce disinfectant concentrates that could be used as an alternative to concentrates based on the active ingredient quaternary ammonium compounds, without the toxicological and ecological disadvantages of these compounds, and without the tendency to develop resistance. The disinfectant concentrates should be easily dilutable with water and suitable for transport as concentrates and for dilution with water in conventional equipment, easily and without requiring specialist knowledge, for subsequent use as surface disinfectants for hard surfaces. Summary of the invention

[0016] The above and other objects are achieved by the disinfectant compositions according to the invention when they contain, as an aqueous disinfectant concentrate, certain carboxylic acids as the active ingredient in addition to certain amino acids, and the disinfectant concentrate is diluted with at least water before use. Quaternary ammonium compounds can then be dispensed with as components of the disinfectant concentrates and thus of the disinfectant compositions. Only the diluted disinfectant compositions obtainable from the disinfectant concentrates are used as surface disinfectants.

[0017] The aim was also to increase the efficacy of these diluted solutions. This would allow the production of concentrates that contain a lower concentration of active ingredients, in this case carboxylic acids, and / or that can be more diluted, yet are still comparable in effectiveness to non-inventive concentrates containing carboxylic acids as active ingredients. This has both ecological and economic advantages.

[0018] The above task was solved by disinfectant concentrates containing, in addition to water - one or more carboxylic acids, namely glycolic acid, tartaric acid, lactic acid and / or benzoic acid, including their salts and - at least one short-chain amino acid, namely glycine, alanine, valine, leucine and / or isoleucine.

[0019] The disinfectant concentrates contain - greater than 50% by weight water; - 0.5 to 10% by weight, in particular 0.9 to 7% by weight, of one or more carboxylic acids selected from one or more members of the group: glycolic acid, tartaric acid, lactic acid and / or benzoic acid and their salts; and - 0.1 to 5% by weight, in particular 0.5 to 3% by weight of one or more amino acids selected from one or more members of the group: glycine, alanine, valine, leucine and isoleucine, in particular glycine;wherein the pH of the disinfectant concentrate is 1 to 2.4, in particular 1.5 to 2.3.

[0020] The amino acids have a pKa value of 2 to 2.4. The pH of the disinfectant concentrates is between pH 1 and pH 2.4, and the pH is preferably equal to or lower than the pKa value of the amino acid used.

[0021] According to a preferred embodiment, the disinfectant concentrate contains at least two of the above-mentioned carboxylic acids, e.g. benzoic acid and one of the acids glycolic acid, tartaric acid or lactic acid or glycolic acid and one of the acids benzoic acid, tartaric acid or lactic acid, or tartaric acid and one of the acids benzoic acid, glycolic acid or lactic acid or lactic acid and one of the acids benzoic acid, glycolic acid or tartaric acid.

[0022] The disinfectant composition is obtainable from the disinfectant concentrate according to at least one of the preceding claims by dilution with water, preferably exclusively with water, with a dilution of preferably 1:4 and more (weight of disinfectant concentrate: weight of water), in particular 1:9 and more, and particularly preferably 1:19 to 1:199.

[0023] Furthermore, in addition to the process for producing the disinfectant composition by dilution, the invention relates to a process for disinfecting hard surfaces with the disinfectant composition by applying it to hard surfaces, in particular by spraying or wiping with soaked mops or cloths, preferably within 24 hours after producing the disinfectant composition from the disinfectant concentrate by dilution with water. Detailed description of the invention

[0024] The disinfectant concentrate may further contain at least one solubilizer, preferably 0.1 to 20% by weight, in particular 2 to 15% by weight.

[0025] The solubilizers are one or more hydrocarbons (e.g. with a total of 3 to 8 carbon atoms) each with ether and / or alcohol and / or ester groups, in particular ether and / or alcohol groups, more preferably each with 3 or 4 or 5 connected carbon atoms (optionally only in one segment or also segments of e.g. 3 plus 3 or 3 plus 4 or 4 plus 4 carbon atoms) and preferably a maximum of 8 carbon atoms per molecule, in particular 1-methoxypropan-2-ol, 1-butoxypropan-2-ol, 1,2-dihydroxypropane and / or 3-methoxy-3-methylbutan-1-ol.

[0026] The disinfectant concentrate may also contain one or more anionic surfactants, in particular fatty alcohol sulfates, fatty alcohol ether sulfates, fatty alcohol sulfonates, and / or olefin sulfonates, preferably sodium lauryl sulfate, sodium lauryl ether sulfate, branched and unbranched alkyl sulfonates, and / or alpha-olefin sulfonates. In addition to or instead of the anionic surfactants, nonionic surfactants, in particular fatty alcohol alkoxylates, may also be present in the disinfectant concentrate.

[0027] In addition, the disinfectant concentrates preferably contain one or more other acids, such as methanesulfonic acid or phosphoric acid, for pH adjustment. Nitric acid, methanesulfonic acid, phosphoric acid, and / or sulfuric acid, especially phosphoric acid, are suitable acidifiers for pH adjustment.

[0028] Acetic acid, propionic acid and / or citric acid can be used as additional carboxylic acids.

[0029] The disinfectant concentrate and the disinfectant composition obtainable from it by dilution do not allow the use of peroxide compounds and, alternatively or additionally, the use of quaternary ammonium compounds can be avoided altogether or can be used only in very small quantities (less than 0.005 wt%).

[0030] According to a preferred embodiment, the disinfectant concentrate further comprises complexing agents, in particular phosphonates, preferably 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) or aminocarboxylates.

[0031] Other added additives may include fragrances, corrosion inhibitors, defoamers and / or cleaning enhancers.

[0032] The pH of the disinfectant concentrate is preferably equal to or less than the pKa value of the amino acid used and, if several amino acids are used, equal to or less than the pKa value of the amino acid with the lowest pKa value.

[0033] The pH of the disinfectant composition is preferably 1.5 to 3.0, more preferably 2.0 to 2.6.

[0034] The disinfectant concentrates should be dilutable using dosing systems, such as those used in hospitals, by connecting appropriate canisters containing disinfectant concentrate and then diluting them with tap water. Experimental part

[0035] It is known that carboxylic acids are less effective against fungi than they are against bacteria and viruses. Candida albicans is the test organism for fungi in Europe. Therefore, Candida albicans was selected as the test organism for the studies. The tests were conducted according to the current European test standard EN 13624.

[0036] Unless otherwise stated, all percentages are by weight. The pH value was measured at 20°C according to CIPAC MT 75.

[0037] In one example, a disinfectant concentrate contained 2.25% glycolic acid, 2.25% lactic acid, and 2.25% sodium benzoate (equivalent to 1.91% benzoic acid). The concentrate also contained surfactants and was adjusted to pH 2.2 with an acid.

[0038] This concentrate was diluted with water to 4%, 2%, 1%, and 0.5%. An additional 0.5% dilution was adjusted to pH 2.4 with further addition of the acid. The dilutions were tested for their efficacy against Candida albicans; the results are summarized in Table 1. Table 1: Active ingredient contents, pH values ​​and reduction factor against Candida albicans of dilutions of a disinfectant concentrate. Concentrate: 2.25% lactic acid, 2.25% glycolic acid, 1.91% benzoic acid PH value Reduction factor [log] 4% solution in water 2,6 > 4,40 2% solution in water 2,7 2,52 1% solution in water 2,9 < 1,03 0.5% solution in water 3,0 < 1,03 0.5% solution in water, acidified 2,4 3,94

[0039] The result is surprising. Although at a pH of 3 or less, the acids are almost exclusively present in their protonated and therefore active form, the 0.5% solution with pH 2.4 was more effective than the 4-fold concentrated 2% solution with pH 2.7.

[0040] One possible solution to increase effectiveness could be to further lower the pH of the concentrate. As a result, the diluted solutions would also have a comparably lower pH. However, this is undesirable. The concentrates are usually diluted in dosing systems. Appropriate canisters of concentrate are connected and then diluted with tap water. The copper pipes in the dosing systems would be corroded by overly acidic concentrates. It has been found that it is advantageous to provide concentrates with the highest possible, material-compatible pH, whose dilution results in the lowest possible pH with high effectiveness and while avoiding chloride ions. Surprisingly, the use of the above-mentioned amino acids has proven beneficial in this regard.

[0041] In another experiment, a disinfectant concentrate containing 0.98 g of glycolic acid, 0.98 g of lactic acid, and 0.98 g of sodium benzoate per 100 g was prepared as an aqueous disinfectant concentrate. The disinfectant concentrate also contained alcohol ethoxylates, anionic surfactants from the alkyl sulfonate group, complexing agents, and solubilizers (especially solubilizers that can also act as defoamers) as non-ionic surfactants.

[0042] The concentrate was prepared with / without the addition of glycine, the pH was adjusted to 1.97 + / -0.02 using 85% phosphoric acid, after which the concentrates were diluted to 5% with purified water and the pH was determined. Table 2: pH values ​​of concentrates and dilutions with / without amino acids pH concentrate pH of a 5% dilution Concentrate without amino acid 1,95 2,74 Concentrate with 0.2 mol / l glycine 1,99 2,39

[0043] The addition of an amino acid, in this case glycine, results in a pH value of the corresponding dilution that is 0.35 lower (see Table 2). Glycine, with its relatively good solubility in water (225 g / l, 20°C), was easy to incorporate, whereas this was not possible with aspartic acid and glutamic acid. Basic amino acids are not suitable for this type of application, as they are typically used commercially as hydrochlorides. The introduction of chloride ions into concentrates within the pH range of the inventive examples leads to significantly poorer corrosion properties.

[0044] Based on these surprising results, a variety of formulations were prepared and tested. The formulations according to the invention and those not according to the invention, as listed below, are identical in terms of excipients.

[0045] The excipients used included non-ionic surfactants from the alcohol ethoxylate group, anionic surfactants from the alkyl sulfonate group, complexing agents, solvents, and the acidifier phosphoric acid. It is important that the excipient composition is identical for all formulations to ensure good comparability. Only the amount and type of carboxylic acids and the proportion of amino acids were varied. Table 3: Examples of concentrates containing an amino acid according to the invention, amounts given in g / 100g. 1a 2a 3a 4a 5a 6a 7a 8a Na benzoate 0,98 0 0 0 0 0 0 0 Tartaric acid 0 0,98 0 0 0,98 0,98 0,98 0,98 Lactic acid 0,98 0,98 0 6,9 0,98 0,98 0,98 0,98 Glycolic acid 0 0 0,98 0 0,98 0,98 0 0 Glycine 1,5 1,5 1,5 1,5 1,5 0,5 0 0 L-Valine 0 0 0 0 0 0 2,3 0 L-Isoleucine 0 0 0 0 0 0 0 2,6 pH 2 2 2 1,5 2 2 2 2 Table 4: Non-inventive examples of concentrates for comparison without amino acid, example 6b only amino acid, amounts given in g / 100g 1b 2b 3b 4b 5b 6b Na benzoate 0,98 0 0 0 0 0 Tartaric acid 0 0,98 0 0 0,98 0 Lactic acid 0,98 0,98 0 6,9 0,98 0 Glycolic acid 0 0 0,98 0 0,98 0 Amino acids 0 0 0 0 0 0 Glycine 0 0 0 0 0 1,5 pH 2 2 2 1,5 2 1,5

[0046] The concentrates were diluted with purified water, the pH was determined, and the efficacy was tested according to EN 13624, "clean conditions," with a contact time of 60 minutes. The results are presented as logarithmic reduction factors.

[0047] The higher this value, the better the effectiveness. To ensure the best possible comparability of the test results, all test samples were subjected to a single test run with the identical initial bacterial suspension. The best effectiveness is described as "total kill" (tk). Here, no microbiological growth was detectable. In this test approach, this meant an effectiveness of at least 4.17 log to a maximum of 6.32 log reduction.

[0048] The results are summarized in Table 5, dilutions according to the invention, and Table 6, dilutions not according to the invention. Table 5: Examples of dilutions from concentrates with an amino acid, pH values ​​and efficacies according to the invention concentrate 1a 2a dilution 5% 4% 3% 5% 4% 3% pH of the dilution 2,26 2,30 2,36 2,20 2,26 2,31 Efficacy, tk or log tk tk tk tk tk tk concentrate 3a 4a 5a 6a 7a 8a dilution 10% 1,5% 5% 3% 3% 5% 5% pH of the dilution 2,08 2,27 2,20 2,23 2,43 2,21 2,19 Efficacy, tk or log tk tk tk tk tk - - - = not measured, tk = "total kill" Table 6: Non-inventive examples of dilutions from concentrates without amino acid, pH values ​​and efficacies and a comparative formulation based only on amino acid. concentrate 1b 2b 3b 4b 5b 6b dilution 5% 5% 10% 1,5% 5% 10% pH of the dilution 2,42 2,48 2,25 2,55 2,58 2,01 Effectiveness, log 4,08 4,12 3,72 <0,8 3,53 <0,8

[0049] In each case, formulations (according to the invention vs. non-inventive) with identical carboxylic acids are to be compared. Comparing 1a 5% with 1b 5%, it is noticeable that 1a 5% is more effective (tk vs. 4.08), and 1a 3%, i.e., a formulation with 40% less active ingredient, is still more effective. The pH increase due to dilution is lower for the inventive formulation 1a 5% than for the non-inventive formulation 1b 5%, and even with the more diluted formulation 1a 3%, the pH is still lower than for dilution 1b 5%. All further comparisons show the same picture: dilutions 2a 5%, 4%, 3% vs. dilution 2b 5%; 3a 10% vs. 3b 10%; 4a 1.5% vs. 4b 1.5%, here at a lower initial pH of the concentrates of 1.5%; 5a 5%, 3% vs. 5b 5%, and also dilution 6a 3% with a lower glycine content of 0.5% still shows an effect vs. 5b 5% with a higher active ingredient content.Formulation 6b was diluted at a lower concentration of 10%, and the concentrate itself was adjusted to a more acidic pH of 1.5 to demonstrate any efficacy of the amino acid itself. This was not the case. 6b at 10% showed no microbiological effect whatsoever. QUOTES CONTAINED IN THE DESCRIPTION

[0000] This list of documents submitted by the applicant was generated automatically and is included solely for the convenience of the reader. This list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions. Cited patent literature

[0000] DE 102015113641 A1

[0009] DE 3229097 C2

[0009] DE 602004008651 T2

[0010] WO 2009096038 A1

[0010] EP 2932985 A1

[0010] WO 2021156297 A1

[0010] US 2023146954 A1

[0010] EP 2781158 B1

[0011] EP 3082433 B1

[0012] EP 3102661 B1

[0013] JP 2019182854 A

[0014] CN 113812419 A

[0014]

Claims

[1] Disinfectant concentrate containing - greater than 50% by weight water; - 0.5 to 10% by weight, in particular 0.9 to 7% by weight, of one or more carboxylic acids selected from one or more members of the group: glycolic acid, tartaric acid, lactic acid and / or benzoic acid and their salts; and - 0.1 to 5% by weight, in particular 0.5 to 3% by weight, of one or more amino acids selected from one or more members of the group: glycine, alanine, valine, leucine, and isoleucine, in particular glycine; wherein the pH of the disinfectant concentrate is 1 to 2.4, in particular 1.5 to 2.

3. [2] Disinfectant concentrate according to claim 1, further comprising at least one solubilizer, preferably 0.1 to 20% by weight, in particular 2 to 15% by weight, wherein the solubilizer is one or more hydrocarbons each having ether and / or alcohol and / or ester groups, in particular ether and / or alcohol group, more preferably each having 3 or 4 or 5 connected carbon atoms and preferably a maximum of 8 carbon atoms per molecule, in particular 1-methoxypropan-2-ol, 1-butoxypropan-2-ol, 1,2-dihydroxypropane and / or 3-methoxy-3-methylbutan-1-ol. [3] Disinfectant concentrate according to claim 1 or 2 further comprising one or more anionic surfactants, in particular fatty alcohol sulfates, fatty alcohol ether sulfates, fatty alcohol sulfonates and / or olefin sulfonates, preferably sodium lauryl sulfate, sodium lauryl ether sulfate, alkyl sulfonates, branched and unbranched, and / or alpha-olefin sulfonates. [4] Disinfectant concentrate according to at least one of the preceding claims, further comprising non-ionic surfactants, in particular fatty alcohol alkoxylates. [5] Disinfectant concentrate according to at least one of the preceding claims, further comprising nitric acid, methanesulfonic acid, phosphoric acid and / or sulfuric acid as acidifying agent for pH adjustment, in particular phosphoric acid. [6] Disinfectant concentrate according to at least one of the preceding claims containing no peroxidic compounds. [7] Disinfectant concentrate according to at least one of the preceding claims containing less than 0.005 wt.% quaternary ammonium compounds, in particular no quaternary ammonium compounds. [8] Disinfectant concentrate according to at least one of the preceding claims, preferably containing at least two of the carboxylic acids according to claim 1 and / or further acetic acid, propionic acid and / or citric acid [9] Disinfectant concentrate according to at least one of the preceding claims, further comprising complexing agents, in particular phosphonates, preferably 1-hydroxyethylidene-1,1-diphosphonic acid, or aminocarboxylates; and / or independently thereof, fragrances, corrosion inhibitors, defoamers and / or cleaning enhancers. [10] Disinfectant concentrate according to at least one of the preceding claims, wherein the pH of the concentrate is equal to or less than the pKa value of the amino acid used and, if several amino acids are used, equal to or less than the pKa value of the amino acid with the lowest pKa value. [11] Disinfectant composition obtainable from the disinfectant concentrate according to at least one of the preceding claims, by dilution with water by 1:4 and more (disinfectant concentrate:water), in particular 1:9 and more, and particularly preferably 1:19 to 1:199, in particular dilution exclusively with water. [12] Disinfectant composition according to claim 11, wherein the pH of the disinfectant composition is 1.5 to 3.0, preferably 2.0 to 2.

6. [13] Disinfectant composition according to at least one of claims 11 or 12 containing no peroxidic compounds. [14] Disinfectant composition according to at least one of claims 11 to 13 containing less than 0.005 wt.% quaternary ammonium compounds, in particular no quaternary ammonium compounds. [15] Process for producing a disinfectant composition according to at least one of claims 11 to 14 from the disinfectant concentrate according to at least one of the preceding claims 1 to 10, by diluting with water, in particular exclusively with water, by 1:4 and more (disinfectant concentrate:water), in particular 1:9 and more, and particularly preferably 1:19 to 1:

199. [16] Method for disinfecting hard surfaces with the disinfectant composition according to at least one of claims 11 to 14 by application to hard surfaces, in particular by spraying or wiping with soaked mops or cloths, preferably within 24 hours after preparation of the disinfectant composition from the disinfectant concentrate according to at least one of claims 1 to 10 by dilution with water.