SK9297Y1 - Disinfectant and its use - Google Patents

Abstract

It is described a long-term stable disinfectant, particularly suitable for disinfection of surfaces, objects or premises in the form of a solution, emulsion, cream, gel, xerogel, suspension, foam, fog or film with bactericidal, sporocidal, virocidal and fungicidal disinfectant efficiency. The disinfectant comprises 0.1 to 25 % by weight Ag+-nitrogen polymer and 0.05 to 3.5 % by weight a quaternary ammonium compound and further may comprise a hydrophilic gel-forming polymer, natural rubber, additives and preservatives, wherein the residue is water.

Description

SK 9297 Υ1

Technical field

The invention relates to a disinfectant suitable for personal disinfection and for disinfecting surfaces, objects or spaces with bactericidal, sporocidal, virocidal and fungicidal disinfectant activity comprising a complex of Ag ⁺ -nitrogen polymer and a quaternary ammonium compound.

Prior art

Antibacterial applications of alcohol-containing disinfectant solutions or gels are widely used, although they have a number of disadvantages, especially when used for long-term disinfection of surfaces and hands. These disadvantages are partially eliminated by silver-containing preparations. The bactericidal effect of silver is due to interactions with the peptidoglycan cell wall and the plasma membrane. The formation of free radicals by silver nanoparticles further causes the cell membrane to be porous and ultimately leads to bacterial cell death. Silver prevents the replication of bacterial DNA by interacting with exposed sulfhydryl groups in bacterial proteins, especially electron transport chain enzymes.

WO2012018888 describes a liquid formulation consisting of a chelated EDTA / Ag and a polyquartemized-69 polymer.

WO2014 / 191631 and US 2019/0083373 to Argenlab applied to Nolla formulations describe a low alcohol (3%) disinfectant foam consisting of water, a foaming agent and an Ag ⁺ -aminopolymer complex prepared by reaction in an anhydrous environment. Examples include the use of an Ag ⁺ -polyethyleneimine complex to prepare a disinfectant foam, in which lactic acid is used to adjust the pH and betaine is used to achieve a moisturizing effect. The silver concentration is 5-2,000 ppm.

Another patent, CA 2846196 from Argenlab applied to Nolla formulations, describes an antimicrobial ionomeric composition consisting of a cationic aminopolymer of silver halide, a stabilizer (inorganic ammonium salts or sulfonamides, saccharin), alcohol and water, and its preparation. The document describes the application of a water-alcohol composition to the surfaces of materials such as metals, wood, cellulose, fibers, hands, paints and textiles.

Nanosilver colloids stabilized with aminopolymers such as polyethyleneimine, polyvinylpyrrolidone, poly (ethylene oxide) -n-poly (2-vinylpyridine) are characterized and described in J. Braz. Chem. Soc., Vol. 28, no. 9, 1608-1618, 2017.

CN102690481 describes a composition consisting of a quartemized ammonium polymer prepared by radical polymerization and silver nanobromide.

WO2018199725 describes a composition prepared from aqueous solutions of silver nitrate and citraconic acid and vinylpyrrolidone followed by UV polymerization.

RU 2402655 describes a natural polymer, silk, impregnated with an aqueous solution of silver nitrate followed by the addition of sodium borohydride. The material is used for the preparation of textiles.

U.S. Pat. No. 20190327976 describes antimicrobial polymethyl methacrylate / silver nanocomposite materials.

US 2018/0311400 describes dressings consisting of an isocyanate-polyester polymer and nanosilver.

Polymer-stabilized and gel-immobilized nanosilver reduction catalysts are described by J. Inorg. Organomet. Polym. DOI 10.1007 / sl0904-016-0373-z. PolyN-vinylpyrrolidone, polyethyleneimine are used as water-soluble polymers.

Nanocomposites of methacrylate polymers prepared by photoinitiated polymerization modified with a secondary amino group and in situ prepared nanosilver are described by J Biomed Mater Res Part B: Appl Biomater, 2011.

For antimicrobial applications, a material consisting of nanocellulose and nanosilver is used (Mohammed, N., Grishkewich, N., Tam, K.C., 2018. Environ. Sci. Nano 5, 623-658).

Gels and films formed from polyurethane-urea and poly (N-isopropylacrylamide-co-acrylic acid-co-butyl methacrylate polymers and coordinated with Ag ^{+ are} described in the Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 47, 4950-4962 (2009 The materials are characterized by AFM, UV, TGA, WA-XRPD and the degree of swelling.

A review article in the International Journal of Antimicrobial Agents 34 (2009) 103-110 describes various antimicrobially active polymer-nanosilver materials.

Three types of nanosilver / polymer nanocomposite materials (polymethyl methacrylate, polystyrene, poly-t-butyl methacrylate) were characterized and studied in terms of Ag particle distribution in Polymer composite, 2009, DOI 10.1002 / pc.20655.

Silver nanomaterials and their polymer composites and their use, preparation and characterization are described in the review article Nanomaterials and Polymer Nanocomposites, https://doi.org/10.1016/B978-0-12-814615-6.00002-3. As polymer matrices, e.g. chitosan, gelatin, polyurethane, nylon 6.

SK 9297 Υ1

Silver nanogels with chitosan are presented by A. S. Grumescu in Antimicrobial nanoarchitectonics: From synthesisto aplications.

Colloidal silver polyvinyl alcohol-polyvinylpyrrolidone gels prepared by repeated freezing are described by YuH, XuX, ChenX, Lu T, Zhang P, Jiang X. J Appl Polym Sci 2007; 103: 125.

A modified guar gum gel impregnated with epicatechin gallate and silver was prepared, characterized and subsequently used for antimicrobially active dressings (International Journal of Nanomedicine 2019: 14 9837-9854).

A thixotropic hydrogel based on clay and an organic modifying agent such as hydroxypropylmethylcellulose, guar hydroxypropyltriammonium chloride, carbomer, xanthan gum and polyvinylpyrrolidone, containing electrolytically obtained sodium hypochlorite, is described in SK 545-2002.

A two-step method for the immobilization of silver nanoparticles consisting in the impregnation of unspecified materials with polyethyleneimine and subsequent immersion of the material in a silver nitrate solution, and its subsequent reduction to nanosilver with polyethyleneimine functional groups is described in CZ303502.

The silver-polyethyleneimine-polylactic acid complex is described in the Journal of Nanomaterials, Volume 2018, Article ID 1048734.

RU 2672869 relates to an antibacterial agent based on a suspension of bacteriophage and silver particles. The reagent is characterized in that it contains a cluster of silver and polyvinylpyrrolidone with the following quantitative content of components: cluster silver, 0.25 - 15.0 mcg / ml, polyvinylpyrrolidone in a final concentration of 0.4 to 0.8 mg / ml, bacteriophage particle suspension 10 up to 10 PFU / ml.

Preparation of input complexes Ag ⁺ -polyethyleneimine, resp. nano Ag-polyethyleneimine by the reaction of silver nitrate, polyethyleneimine and optionally inorganic acid and ascorbic acid is described in Materials Science and Engineering C 42 (2014) 31-37, Journal of Photochemistry & Photobiology, B: Biology 173 (2017) 508-513, Int. J. Environ. Res. Public Health 2016, 13, 334, ACS Omega 2018, 3, 16721-16727. Thermal preparation by reacting silver nitrate with polyethyleneimine is reported in Journal of Nanomaterials, Volume 2018, Article ID 1048734.

The essence of the technical solution

The Ag ⁺ -nitrogen-free polymer complex is effective only against some microorganisms from the group of gram-positive bacteria, and high concentrations of this complex must be used against other strains or fungi and viruses. In addition, it has been found that in aqueous or aqueous-alcoholic formulations, stability problems are consequently caused by agglomeration of the active ingredient by a concentration gradient. In general, there is a lack of broad-spectrum disinfectants providing not only immediate disinfection but also effective long-term disinfection, which should show long-term stability, i. is the desired efficacy in the order of several weeks to months when applied at low concentrations. These requirements are met by a disinfectant according to the present invention comprising a composition comprising a complex of Ag ⁺ -nitrogen nitrogen and a quaternary ammonium salt in an aqueous or aqueous-organic medium.

The technical solution therefore relates to a disinfectant containing 0.1 to 25% by weight. complex Ag ⁺ -nitrogen nitrogen containing 0.0001% to 0.75% (1 to 7,500 ppm) of silver and 0.05 to 3.5 wt. a quaternary ammonium compound selected from the group consisting of N-C8-C18-alkyl-benzyldimethylammonium chloride, N-di (C8-C18-alkyl) dimethylammonium chloride, {[3- (dodecanoylamino) propyl] (dimethyl) ammonio} acetate or lauramidpropyl betaine, wherein said amount of individual components is based on the weight of the disinfectant and the rest of the composition is water. A broad-spectrum disinfectant is obtained, the effective concentration of the active ingredients being unexpectedly low, of the order of only tens of ppm. The addition of at least one quaternary ammonium compound in an amount of 0.05 to 3.5% by weight. to the Ag ⁺ -nitrogenous polymer complex provides a long-term effective disinfectant according to EN 1276 and EN 1650 standards, this agent being effective after only 30 seconds. Polyethyleneimine, polyvinylpyrrolidone, polyvinylamine, polyaminopropyl biguanidine, polyhexamethylene biguanidine, polyacrylamine, polyarylamine or mixtures thereof can be used as nitrogen polymers. All starting nitrogen polymers are commercially available. Another advantage is that some Ag ⁺ -nitrogen polymer complexes as well as quaternary ammonium salts are commercially available.

Furthermore, it has surprisingly been found that when a composition of a complex of Ag ⁺ -nitrogen nitrogen and a quaternary ammonium salt is bound to a matrix of gel-forming material, compositions with high stability and the possibility of variability of the final formulation are obtained under very mild thermal conditions. In particular, hydrophilic gel-forming polymers, such as e.g. cellulose, carboxymethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, hemicellulose, polyvinyl alcohol, chitosan, pectin, betaglucan, collagen, gelatin, polyethylene oxide and / or its copolymers, polypropylene oxide and / or its copolymers and / or its copolymers copolymers, polyacrylic acid and / or its derivatives and copolymers, synthetic and / or natural starches, or combinations thereof.

SK 9297 Υ1

The amount of hydrophilic gel-forming polymer in the disinfectant ranges from 0.2 to 35% by weight, based on the weight of the composition. Natural polysaccharides in particular are preferably used for the formation of such matrices. Furthermore, it is possible to harmonize the desired properties of the matrix by adding natural rubber or in combination with another polysaccharide in different proportions of the individual components of the matrix. Particularly suitable are combinations of gelling material with natural gum, wherein the natural gum is selected from the group consisting of glucomannan, xanthan gum, gellan, guar gum, acacia, arabinogalactan, carobine, laminarin, agar, carrageenan, alginate and / or its salts, or their salts. combination, and wherein the amount of natural gum is 0.5 to 10% by weight, based on the weight of the disinfectant. These forms can be prepared into formulations of different viscosities. The hydrating and adhesive properties of the prepared formulations to the skin are exceptional due to the natural polymers used. The advantage of the solution is also the easy transformation of the gel into a solid form, such as xerogel, film or alcohol. Such procedures, e.g. lyophilization, are routinely used and described in the literature. The matrix stabilizing the silver particles and / or ions can be prepared separately, for example as a gel, xerogel or film, followed by impregnation with a silver component, or the silver component of the preparation is added directly to the medium for preparing said matrices. j. gels, xerogels or films. Such a material has an advantage over solutions in its ability to be fixed for a long time in addition to its ability to penetrate easily. Another advantage of the polysaccharides used is the biodegradability of the matrix and the zero load in terms of metabolites. The product has excellent long-term effectiveness, is environmentally friendly and has a practically 100% degradable matrix.

The disinfectant according to the invention may further contain additives in an amount of 0.05 to 10% by weight, based on the weight of the disinfectant, selected from the group consisting of betaine, glucoprotamine, antimicrobial essential oils, hyaluronic acid, lactic acid, citric acid, glycolic acid, glutaraldehyde , nonionic surfactants, ethanol, 2-propanol, glycerin, Aloe vera or urea, or combinations thereof and preservatives in an amount of 0.01 to 3% by weight, based on the weight of the disinfectant.

The disinfectants according to the invention can be in the form of a solution, hydroemulsion, hydrocream, gel, hydrogel, xerogel, suspension, emulsion, foam, mist or film and can be used to disinfect surfaces, objects, materials, wounds, persons, hands and / or premises.

Disinfectants according to the technical solution also have a high affinity for different types of surfaces, e.g. paper, leather, wood, metal, textiles, forming a thin transparent layer on the sanitary surface, stable against UV radiation, without corrosive or keratolytic properties. The mentioned technical solution represents an advantage also in terms of possible toxicity, allergy, resp. environmental burden. The disinfectants according to the present technical solution are also non-aggressive for the skin and disinfected surfaces.

Further advantages as well as details of the formulation, application as well as the effectiveness of the disinfectant according to this technical solution are apparent from the examples of the technical solution without being limited to them.

Examples of embodiments

Example 1

To a solution of 1 g of Ag ⁺ -polyethyleneimine complex (containing 4,200 ppm Ag) in 198 ml of water was added 0.3 g of urea and at 35 ° C gradually and with vigorous stirring 0.1 g of didecyldimethylammonium chloride and 0.03 g of thymol. . After cooling to room temperature, the resulting material was evacuated for 15 minutes at room temperature. After dilution with ethanol in a ratio of 1: 3, a clear solution without opalescence is obtained, which by nebulization gives a fine mist.

Example 2

To a solution of 5.3 g of carboxymethyl cellulose in 200 ml of water and 2 g of Ag ⁺ -polyethyleneimine complex at 85 DEG C. were added 0.8 g of potassium aluminum sulphate to initiate gel formation and 0.25 g of C12-C16 alkyldimethylbenzylammonium chloride. The mixture was stirred vigorously for 15 minutes while cooling to form a gel.

Example 3

To a solution of a mixture of 4 g of polyvinyl alcohol and carboxymethylcellulose (1: 1) in 100 ml of water was added 1 g of Ag ⁺ -polyethyleneimine complex and 0.15 g of dimethyldioctadecylammonium chloride at 80 ° C. With stirring for 30 minutes, the mixture was cooled to 20 ° C and then subjected to two freezing cycles of 24 hours at -20 ° C and 4 hours at 25 ° C. A clear hydrogel was obtained, which was transferred to lyophilization vessels and dried in a lyophilizer for 24 hours. 4.2 g of powdered xerogel with a water content determined by the Karl Fischer method of 0.42% were obtained.

SK 9297 Υ1

Example 4

0.25 g of C12-C16 alkyldimethylbenzylammonium chloride, 2 g of sodium alginate, 1 g of carboxymethylcellulose and 0.5 g of glycerol were added successively to 150 ml of water at 65 ° C. After dissolution, 100 ml of 3% acetic acid were added, followed by 1.5 g of chitosan (degree of deacetylation <90%). The mixture was refluxed until clear. ^{1.5 g of Ag +} -polyethyleneimine complex and 0.25 g of polyaminopropyl biguanidine were added to the stirred solution, and the mixture was poured into petri dishes and dried at 75 ° C. The material was overlaid with 100 mL of 3% CaCl ₂ solution, allowed to act for 30 minutes, then decanted and dried at 45 ° C in a vacuum oven. 4.1 g of a thematic antibacterial film were obtained.

Example 5

To a solution of 1 g of Ag ⁺ -polyethyleneimine complex (content 4,200 ppm Ag) in 99 ml of water was added 1 g of glycerol and at 65 ° C gradually with vigorous stirring 1.5 g of hydroxypropyl methylcellulose followed by 0.1 g of lauramidpropyl betaine. After cooling to room temperature, the resulting material was evacuated for 15 minutes at room temperature. A clear hydrogel was obtained. Antimicrobial activity was tested according to ENI 1500 on a strain of Staphylococcus aureus, at 20 ° C, contact time 60 seconds. The initial KTJ value (KTJ = colony forming unit) for Staphylococcus aureus was 3.5 x 10 ⁷ , after the contact time the log reduction was found to be 7, which means that the tested hydrogel has a high bactericidal activity.

Example 6

The procedure was analogous to Example 5, except that the Ag ⁺ -polyethyleneimine complex was used at a concentration of 0.012% by weight. Ag, 0.3 wt. benzalkonium chloride and 0.2 wt. carbomer 276.

Example 7

The procedure was analogous to Example 5, except that the Ag ⁺ -polyethyleneimine complex was used at a concentration of 0.012% by weight. Ag and 0.25 wt. benzalkonium chloride. The sample was analyzed using the methods according to EN 1276: 2019 and EN 1650: 2019, the results are in Table 1.

Table 1

The strain used Amount of CTU / ml Contact time 30 s Contact time 60 s Incubation Concentration% (V / V) No dilution Staphylococcus aureus CCM 4516 N No On the Log R 2.8 x 10 ⁸ 2.8 x 10 ⁷ <10 7 2.8 x 10 ⁸ 2.8 x 10 ⁷ <10 7 24 h / 36 ± 1 ° C Pseudomonas aeruginosa CCM 1961 N No On the Log R 3.5 x 10 ⁸ 3.5 x 10 ⁷ <10 7 3.5 x 10 ⁸ 3.5 x 10 ⁷ <10 7 24 h / 36 ± 1 ° C Escherichia coli CCM 3988 N No On the Log R 3.9 x 10 ⁸ 3.9 x 10 ⁷ <10 7 3.9 x 10 ⁸ 3.9 x 10 ⁷ <10 7 24 h / 36 ± 1 ° C Enterococcus hirae CCM 4533 N No And Log R 4 x 10 ⁸ 4 x 10 ⁷ <10 7 4 x 10 ⁸ 4 x 10 ⁷ <10 7 24h / 36 ± 1 ° C Candida albicans CCM 8215 N No 4.3 x 10 ⁷ 4.3 x 10 ⁶ 4.3 x 10 ⁷ 4.3x 10 ⁶ 24 h /

SK 9297 Υ1

On the Log R <10 6 <10 6 30 ± 1 ° C Aspergillus niger / brasiliensis / CCM 8222 N No On the Log R - 2.8 x 10 ⁷ 2.8 x 10 ⁶ <10 6 48 h / 30 ± 1 ° C

Note: Results of KTJ concentration reduced by 5 decimal places expressed logarithmically (Log R) are bactericidal. The KTJ concentration results reduced by 4 decimal places expressed logarithmically (Log R) are fungicidal or yeastcidal.

Example 8

The procedure was analogous to Example 1, except that an Ag ⁺ -polyvinylpyrrolidone complex of 0.012% by weight was used. Ag.

Industrial applicability

According to the mentioned technical solution, it is possible to industrially produce a disinfectant suitable for disinfecting persons and for disinfecting e.g. veterinary premises, interiors of buildings, floors, workplaces, but also swimming pools, wellness, saunas and for the preparation of products such as disinfectant soaps, etc., in the form of gel, xerogel, aqueous solution, film, mist with bactericidal, sporocidal, virocidal and fungicidal disinfectant effectiveness. As the composition does not have corrosive effects, it can also be used effectively to disinfect small metal objects, e.g. refrigerators, and appliances, e.g. in healthcare and food.

Claims (8)

SK 9297 Υ1 CLAIMS FOR PROTECTION Disinfectant composition, characterized in that it contains 0.1 to 25% by weight, based on the weight of this composition, of an Ag ⁺ -nitrogen polymer complex containing 0.0001 to 0.75% by weight. silver and 0.05 to 3.5% by weight, based on the weight of the composition, of a quaternary ammonium compound selected from the group consisting of N-C8-C18-alkyl-benzyldimethylammonium chloride, N-di (C8-C18-alkyl] dimethylammonium chloride, [3- (dodecanoylamino) propyl] (dimethyl) ammonio} acetate or lauramidepropyl betaine and the remainder of the composition is water. Disinfectant according to claim 1, characterized in that the nitrogenous polymer is selected from the group consisting of polyethyleneimine, polyvinylpyrrolidone, polyvinylamine, polyaminopropyl biguanidine, polyhexamethylene biguanidine, polyacrylamine, polyarylamine or mixtures thereof. Disinfectant composition according to claims 1 or 2, characterized in that it further comprises a hydrophilic gel-forming polymer in an amount of 0.2 to 35% by weight, based on the weight of the composition, selected from the group consisting of cellulose, carboxymethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose , hydroxypropylmethylcellulose, hemicellulose, polyvinyl alcohol, chitosan, pectin, betaglucan, collagen, gelatin, polyethylene oxide and / or its copolymers, polypropylene oxide and / or its copolymers, polylactic acid and / or its derivatives and copolymers, polyacrylic acid and its derivatives and copolymers, synthetic and / or natural starches, or combinations thereof. The disinfectant composition of claim 3, further comprising natural gum in an amount of 0.5 to 10% by weight based on the weight of the composition selected from the group consisting of glucomannan, xanthan gum, gellan, guar gum, acacia. , arabinogalactan, carobine, laminarin, agar, carrageenan, alginate and / or its salts, or combinations thereof. Disinfectant composition according to any one of the preceding claims, characterized in that it further comprises additives in an amount of 0.05 to 10% by weight, based on the weight of the composition, selected from the group consisting of betaine, glucoprotamine, antimicrobial essential oils, hyaluronic acid, acid lactic acid, citric acid, glycolic acid, glutaraldehyde, nonionic surfactants, ethanol, 2-propanol, glycerin, Aloe vera or urea, or combinations thereof and preservatives in an amount of 0.01 to 3% by weight. based on the weight of the composition. Disinfectant according to any one of the preceding claims, characterized in that it is in the form of a solution, hydroemulsion, hydrocream, gel, hydrogel, xerogel, suspension, emulsion, foam, mist or film. Use of a disinfectant according to any one of the preceding claims for disinfecting surfaces, objects, materials and / or premises. Method for disinfecting surfaces, objects of materials and / or spaces, characterized in that a disinfectant according to any one of claims 1 to 6 is applied to the disinfected surface, object, material and / or to the disinfected space. End of document