RU2540478C1 - Composition for preparing antimicrobial coating - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: what is described is a composition for an antimicrobial coating containing inorganic substance nanoparticles, an active substance, a binding agent and a solvent. As the inorganic substance, the composition contains silicone dioxide; the active substance is presented by a mixture of quaternary ammonium compound and chlorhexidine; the solvent is a mixture of ethyl cellosolve and butyl cellosolve; the binding agent is a mixture of polymethylphenylsiloxane resin and butyl/methyl methacrylate copolymer in the following proportions, wt %: butyl/methyl methacrylate copolymer 1.70-10.0, polymethylphenylsiloxane resin 5.0-20.0, silicone dioxide 0.5-3.0, chlorhexidine (20% aqueous) 3.0-8.0, quaternary ammonium compound 0.5-3.0, ethyl cellosolve 20.0-50.0, butyl cellosolve to 100%.

EFFECT: providing the water-stability of the long-action antimicrobial coating, ecological safety and applicability for porous surface finish.

4 cl, 5 tbl, 1 ex

Description

The invention relates to medicine, being a coating that allows for long-term antimicrobial protection of porous surfaces, for example plastered surfaces of walls and ceilings, concrete surfaces or surfaces made of natural or artificial stone, as well as metal and plastic, surfaces painted with water-emulsion or latex paints , ceramic surfaces, etc., as well as surfaces that do not tolerate contact with water, for example, from synthetic composite materials (MDF, particle board), wood x materials, surfaces, colored chalk, lime or similar materials.

Known antimicrobial organosoluble coatings obtained by the use of film-forming antimicrobial agents, for example, in the form of Septopag varnish (TU 9392-028-41547288-2004 "Antimicrobial agent for surfaces of SEPTOPAG") containing polyhexamethylene guanidine hydrochloride (PGM) as an active component compatible with other components of the paint composition - chlorosulfonated polyethylene and petroleum solvent (Nefras A) or in the form of a paint and varnish coating, for example BIOKRAPAG-2 antimicrobial paint (TU 2312-002-41547288-1999 "E Ali Nitrocellulose "BIOKRAPAG-2") from the same active component based enamels PF-115.

Known compositions have a wide range of bactericidal and fungicidal activity and can be used to treat various surfaces as a primer or topcoat. When salts of PHMG are added to paints and varnishes (coatings), there is a problem of their compatibility with various coatings, paint bases and film-forming agents, since these salts are soluble in water and lower alcohols, but not soluble in organic solvents used in coatings, which limits the possibility of their use. use in organo-dilutable coatings. Moreover, PHMG is a moderately toxic substance (hazard class 3), exhibits a general toxic and irritating effect, the severity of which directly depends on the level and duration of exposure (Abstract of the dissertation by N.V. Muratova for the degree of candidate of medical sciences “Toxicological and hygienic aspects of action polyhexamethylene guanidine hydrochloride, a new preparation of the polyguanidine series. ”- Irkutsk, 1994). In scientific circles, disputes are ongoing about the toxicity of this drug, including its ability to cause toxic hepatitis.

In this regard, promising directions for the creation of bactericidal compositions are compounds based on quaternary ammonium compounds (QAS), for example, alkyl dimethylbenzylammonium chloride, veltab (a quaternary ammonium compound clathrate with carbamide), chlorhexidine gluconate, and other proven antiseptics. However, aqueous or alcoholic solutions of these antiseptics do not exhibit a prolonged action. To increase the duration of the action of bactericidal preparations, nanosized particles with a diameter of the order of several nanometers (1 nm = 10-9 m) of an inorganic sorbent are introduced into the compositions to incorporate the active component into its structure with subsequent release during operation or the introduction of nanosized metal particles with biocidal properties, or the introduction of chemically modified organic binders.

So, for example, a composition for disinfecting a solid surface is known, which is an aqueous colloidal dispersion, which contains an inorganic sorbent for incorporating the active component - silicon dioxide nanoparticles with sizes from 1 to 100 nm, contains at least one quaternary-based biocide as an active component. ammonia, with a ratio of silicon dioxide to quaternary ammonium from 5 × 10 ^-5 : 1 to 1.1, as well as organic solvents miscible with water, which are used as alcohols, diols, glycols, ethers g glycol, alkylene glycol ethers and mixtures thereof in an amount of from 0.1 to 5 wt% (US patent No. 2006/0269441, IPC A61L 2/18, 2006). The composition is sprayed onto the surface or non-woven napkins made of various fibers are impregnated with it. The use of a known composition allows disinfection by surface treatment with an aqueous solution of a colloidal dispersion, which forms a thin film. However, in the absence of a film-forming substance in contact with water, the activity of a known composition is lost, and therefore, an effective prolonged antiseptic effect is not provided. Moreover, it is not intended for the treatment of surfaces that do not tolerate contact with water.

The known composition of the biocidal composition, consisting,%: composite, which is a product of the interaction of 10-15 wt.h. cationic water-soluble polymer and 1-5 parts by weight nanoparticles of at least one metal oxide selected from the group consisting of zinc oxide, zirconium oxide, cerium oxide, titanium oxide 30-50, a nanoparticle stabilizer selected from the group comprising alkoxyalkyl substituted silane, alkylenediamine, cationic surfactant, neutral surfactant active substance 0.5-5 and water 49.5-69.5 (patent RU No. 2398804, 2010).

The known composition has insufficient biocidal properties, especially in relation to Staphylococcus aureus, which limits its use in children's and medical institutions.

A known composition of a film antiseptic protective coating for inorganic materials and synthetic polymers, consisting of a mixture of a polymer complex of dimethylalkylbenzylammonium chloride containing an alkyl group from C ₈ to C ₁₆ , with a copolymer of styrene with maleic anhydride, which was previously subjected to chemical modification to open anhydride cycles with the formation of carboxylate groups with polyvinyl butyral at their ratios, wt.%: antiseptic polymer 25-50; polyvinyl butyral 50-75 (Patent RU No. 2445980, IPC A61L 101/46, A61L 2/16, 2012).

The known composition provides the possibility of obtaining an antiseptic film coating of prolonged action, where the Quaternary ammonium salt - catamine AB is used as the active component. The resulting coating is water resistant, i.e. cannot be washed off with water. However, the manufacture of a known composition requires the use of toxic organic solvents, i.e. the operation of coatings containing a significant amount of film-forming is accompanied by the evaporation of solvent and polystyrene degradation products into the atmosphere. Moreover, its replacement and removal also requires a significant amount of toxic solvents, which limits the use of known compounds in medical and child care facilities, in veterinary institutions. Moreover, the known composition can be used for processing metals, ceramics and materials from synthetic polymers and is not intended for the treatment of porous surfaces (grouting, plastered, concrete and cement surfaces, etc.).

Closest to the proposed is a composition for biocide coatings containing a binder base in the form of a paint or film-forming material, a biocidal additive with a nanostructured particle size, which is used as 0.5-10 wt.% Modified bentonite in the form of montmorillonite with a nanoparticle size of 2- 500 nm, in which alkali metal ions during the modification of bentonite with a solution of catamine AB, alkali metal ions are replaced by cations of the latter [CnH 2n + 1N + (CH ₃ ) 2CH ₂ C ₆ H ₅ ], where n = 10-18 and 0.001-0.5 wt.% capsaicin (patent RU No. 2338765, 2008). As a paint and varnish material, organosoluble styrene, alkyd, epoxy, pentaphthalic bases or water-emulsion bases or film-forming materials, such as drying oil, are used.

Known compounds are difficult to prepare, contain expensive capsaicin, which when exposed to skin can be irritating.

The objective of the present invention is to expand the arsenal of waterproof antimicrobials of prolonged action with increased efficiency, having environmental safety and providing the ability to use for processing preferably porous surfaces in enclosed spaces intended for the provision of medical care, in child care facilities, in residential premises, rooms for maintenance and treatment animals and in other rooms.

EFFECT: provision of water resistance of an antimicrobial coating of prolonged action, ensuring environmental safety and the possibility of using porous surfaces for processing.

The problem is solved in that a composition for producing an antimicrobial coating is proposed, including nanoscale particles of an inorganic substance, an active substance, a binder and a solvent, characterized in that it contains silicon dioxide as an inorganic substance, contains a mixture of a quaternary ammonium compound and chlorhexidine as an active substance, as a solvent it contains a mixture of ethyl cellosolve and butyl cellosolve, and as a binder it contains a mixture of polymethylphenylsiloxane resin and a copolymer of butyl methacrylate and methyl methacrylate in the following ratio of components, wt.%:

copolymer of butyl methacrylate and methyl methacrylate 1.70-10.0 polymethylphenylsiloxane resin 5.0-20.0 silica 0.5-3.0 chlorhexidine (aqueous 20%) 3.0-8.0 quaternary ammonium compound 0.5-3.0 ethyl cellosolve 20.0-50.0 butyl cellosolve up to 100

As a silicon dioxide powder, AEROSIL can be used, which is commercially available according to GOST 14922-77, for example, grades A-150, A-200, A-300 (unmodified) or R805, R972 (hydrophobic), which have particle sizes from 5 nm to 40 nm (nanoparticles).

As solvents, ethyl cellosolve is used according to GOST 8313-88, which is ethylene glycol monoethyl ether, and butyl cellosolve, manufactured according to TU 6-01-646-84.

As a binder, a copolymer of butyl methacrylate and methyl methacrylate, manufactured on an industrial scale, for example, under the trademark NeoCryl B-725, and a polymethylphenylsiloxane resin, manufactured on an industrial scale, for example, according to TU 2228-277-05763441-99, also known as Lac PMFS, are used. As a mixture of these binders, a finished mixture manufactured on an industrial scale under the brand of Lac KO-085 according to TU 6-02-753-78 can be used.

As the active component, chlorhexidine 1,6-Di- (para-chlorophenylguanido) -hexane is used. Available in the form of a bigluconate (Chlorhexidini bigluconas), -20% aqueous solution. Indicated topically and externally as an antiseptic in the form of aqueous or aqueous-alcoholic solutions, including for the treatment of mucous tissues.

As the active component, a quaternary ammonium compound (HOUR) of the general formula is used:

where R, R ¹ , R ² , R ³ are organic substituents:

methyl-; benzyl or alkyl C ₁₀ -C ₁₈ ;

X - chloride or bromide

or general formula:

where R, R ¹ , R ² , R ³ are organic substituents:

methyl-; benzyl or alkyl C ₁₀ -C ₁₈ ;

X is chloride or bromide;

in the form of a clathrate with urea.

As the aforementioned HOURs, for example, dialkyl dimethyl ammonium bromide, C ₁₄ -C ₁₈ , dialkyldimethyl ammonium bromide, C ₁₀ -C ₁₂ urea clathrate, alkyl benzitrimethyl ammonium chloride, C ₁₂ -C ₁₄ , alkyl trimethyl ammonium, C ₁₂ -C ₁₄ chloride, alkyl , C ₁₂ -C ₁₄ bromide, or a combination thereof or other similar compounds, for example, Veltab, which is an HAC-clathrate of a quaternary ammonium compound with urea produced on an industrial scale by CJSC "VELT" (Russia), or its analogues containing ChAS-Veltogran, Asenol Face Eid, Lactasept, MDS-2.

The inventive composition is prepared as follows. About half of the declared amount of the solvent mixture is mixed with the declared amount of the active component, which is used as a mixture of HOUR and chlorhexidine in the presence of silicon dioxide powder, which is used Aerosil. The suspension is mixed mainly using ultrasonic treatment, which can be carried out, for example, by an ultrasonic device of the brand UZDT-125 in normal mode for preferably 15-20 minutes at a temperature of the working room. The second half of the solvent mixture is mixed with a mixture of binders, the resulting mixture is added to a suspension of silicon dioxide and subjected to homogenization by ultrasonic treatment for 5-7 minutes. The resulting composition is used for processing walls, ceilings, grouting, etc. surfaces by spraying or by brushing or any other known method. Application of the inventive composition is carried out once in a continuous layer on a prepared dry surface at a temperature not lower than +5 C and not higher than +35 C with a relative humidity of not more than 75%.

Application is carried out using a standard aerosol can, special spray equipment according to the passport data and instructions for their use (consumption rate 45 g / m ² ), a soft flat brush or roller (consumption rate 50 g / m ² ). When performing work on applying the claimed composition, the actual consumption depends on the qualifications of the personnel, application methods, equipment used, condition and type of surface and other conditions, and may deviate from the norm by 10-50%.

The drying time of the coating depends on the following factors: temperature, relative humidity, ventilation. High humidity, low temperature, and poor ventilation slow down the drying process and may interfere with the adhesion of the coating to the substrate. Therefore, it is necessary to provide the most favorable conditions for coating. Providing the necessary conditions, the drying time is 3 hours.

Drying of the coating is carried out in vivo. At an ambient temperature of (25 ± 5) ° C and a relative humidity of 75%. The coating dries quickly, forming a transparent thin film.

After the set time for drying, washing off of the claimed composition with wet processing does not occur.

Full operational properties, the surface covered by the claimed composition, acquires after 3 days.

The control of coating formation is carried out visually with natural or artificial daylight diffused light. The coating should be solid, transparent, homogeneous, even, without cracks, blisters.

Comparison of the proposed method with the prototype allows us to conclude that the criterion of "novelty".

In science and technology, the use of HOURs and their combinations as a disinfectant with the achievement of bactericidal (in relation to gram-negative and gram-positive bacteria), fungicidal and virucidal activity is known. The use of chlorhexidine as a bactericidal agent is also known. The use of a mixture of HOUR and chlorhexidine in the claimed composition allows to increase the antimicrobial activity of the new drug and to ensure its prolonged action in the treatment of solid, preferably porous, wood surfaces, cement joints, plastered surfaces, etc.

The new technical result can be explained by the fact that when silicon dioxide nanoparticles are mixed under ultrasonic exposure (sonication), hydrophilic silicon oxide particles create a stable colloidal system in which silicon dioxide particles are not subject to agglomeration, i.e. each particle becomes available for subsequent interaction with HOUR and chlorhexidine. Ultrasonic exposure of a mixture of silicon dioxide - a mixture of QAS with chlorhexidine leads to the fact that during sorption and electrostatic interaction of positively charged particles of QAS with negatively charged nanoparticles of silicon dioxide, a stable complex is formed, the antimicrobial activity of which turned out to be higher than the activity of pure QAS. In this case, the activity of the composition obtained by the claimed method remains for a long time, because the binder used ensures uniform release of the active component, does not block its action, i.e. provides a prolonged action of the coating formed during drying of the composition on the treated surface. The solvent used ensures the stability of the claimed composition to delamination for 12 months, preventing the crystallization of the active component, i.e. the initial properties of the composition are retained for a long time. Moreover, it is the claimed mixture of solvents in the indicated interval value that provides a synergistic effect from the use of a mixture of active components sorbed on silicon dioxide nanoparticles.

The claimed technical result explicitly does not follow from the knowledge known in science and technology, i.e. is unobvious. Therefore, there is reason to conclude that the claimed invention meets the criterion of "inventive step".

The inventive composition can be manufactured using substances and equipment known in science and technology, i.e. The claimed technical solution meets the criterion of "industrial applicability".

The inventive composition is illustrated by the following examples of specific performance.

Example 1 (according to the invention)

Half of the required amount of a mixture of ethyl cellosolve and butyl cellosolve is poured into the container, the required amount of chlorhexidine in the form of a 20% aqueous solution and HOUR, which is taken as Veltab, and Aerosil A-150 powder, are mixed with each other under ultrasonic action of UZDP-125 with a capacity of 100 W for 15 minutes at the temperature of the working room, receiving a suspension of the nanocomposite. In another container, the second half of the required amount of a mixture of ethyl cellosolve and butyl cellosolve is mixed with the required quantities of a copolymer of butyl methacrylate and methyl methacrylate of the brand NeoCryl B-725 and polymethyl phenylsiloxane resin - Lac PFMS. The resulting binder solution is added to the suspension of the nanocomposite and mixed with each other under the conditions of ultrasonic treatment of ultrasonic treatment device-125 with a power of 100 W for 5 minutes at the temperature of the working room to obtain the claimed composition. These components are taken in the following ratio, wt.%

copolymer of butyl methacrylate and methyl methacrylate 1.7 polymethylphenylsiloxane resin 16.7 ethyl cellosolve thirty butyl cellosolve 42.3 silica 1.3 chlorhexidine (aqueous 20%) 6.7 quaternary ammonium compound 1.3

The effectiveness of the disinfecting antibacterial effect of coatings based on the obtained nanocomposite was evaluated in relation to the most relevant causative agents of nosocomial infections.

For the study used slides coated with a disinfectant coating based on a nanocomposite, as well as solutions containing the claimed composition. The study of the disinfecting effect was carried out using nosocomial antibiotic-resistant microbial strains of microorganisms (Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter spp.) By applying working dilutions of cultures of these microorganisms on the surface with appropriate coatings.

Preparation of working dilutions of the studied crops. From daily cultures of these microorganisms grown on beveled meat and peptone agar, stock dilutions were prepared in which the concentration of living cells was determined by titration. To determine the working concentrations, 50 μl of each successive ten-fold dilution was made by suspension of microorganisms in Petri dishes with nutrient medium (Müller-Hington) and cultured for 24 hours at 37 ° C, after which the number of colonies formed in each dish was counted. After determining the concentration of microorganisms in stock dilutions, working culture dilutions were prepared on the basis of the formation on the surface of agar in a Petri dish with 50 μl of 500-1000 colonies inoculated.

The study of the antibacterial activity of liquid samples was carried out by determining the residual infectious activity of test cultures after exposure to solutions containing decreasing concentrations of composites. The results of the evaluation of bactericidal activity are shown in table 1.

As can be seen from the data in table 1, the coatings obtained from the inventive nanocomposite have a pronounced bactericidal effect in relation to the studied strains.

Verification of the biocidal action of the obtained nanocomposite sample was carried out in accordance with the requirements of "P 4.2.2643-10. 3.5. Disinfection. Methods of laboratory research and testing of disinfectants to assess their effectiveness and safety. Leadership ”(approved by Rospotrebnadzor on 06/01/2010). The following test cultures were used: Staphylococcus aureus ATCC 6538-P, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 9027, Klebsiella pneumoniae ATCC 43816, Enterobacter agglomerans ATCC 13460, Aeromonas hydrophila ATCC 7966, ATigiachomatis 8 Chlamychida .

A poorly water-soluble nanocomposite sample was studied deposited and dried on hard surfaces (slides) by imprinting on sterile and non-sterile agar in Petri dishes at room temperature 25 ° C and 37 ° C. The growth of microorganisms was recorded after 24 hours.

As the study showed, germination of all samples was observed by colonies of microorganisms only at a temperature of 37 ° C, regardless of the sterility of the culture medium directly around the glass with an antimicrobial coating. Using the diffuse method, the antimicrobial activity of the sample was studied.

To determine the antimicrobial effect of the sample by agar diffusion using wells in 100 ml of molten and cooled to 60-65 ° C nutrient agar medium, 0.5 ml of a suspension of the diluted standard suspension was added and 20 ml were poured into Petri dishes. After solidification, the cups were dried for 30 minutes and made at a distance of 28-30 mm from the center around the cup circumference, three holes with a diameter of 8 mm (special tool). Prepared sample solutions were placed in the wells. The growth of microorganisms was evaluated by measuring the diameter of the zones of absence of growth of microorganisms in mm. The data obtained are presented in table 2.

As can be seen from table 2, the inventive composition shows satisfactory antimicrobial activity in the initial concentration (without dilution).

The duration of the antimicrobial activity of the sample was studied simultaneously four times by the methods of disco-diffusion and diffusion into agar using wells in Petri dishes, with unlimited time exposure. The data are presented in table 3. As can be seen from table 3, the water-insoluble nanocomposite according to example 1 shows pronounced biocidal properties, while the antimicrobial properties are stored for a sufficiently long time (up to 14 days) in the form of a solid dry coating, which mainly distinguishes these samples from the known antimicrobial agents (in particular HOURS) that lose antimicrobial activity after drying.

In addition, to test the duration and effectiveness of the biocidal action of the claimed sample in the form of a coating, field trials were conducted. The inventive composition was applied by spraying from a spray gun onto a ceramic tile of a public toilet to form a coating. Washings were performed (within 5 months at equal intervals of 1 month) on transport media for inoculation on nutrient media to determine the germination of microorganisms and using bacterial prints (HiMedia) to calculate the microbial number (provided the germination of the bacterial prints). Data on the duration and effectiveness of biocidal action are shown in table 4.

As a control, similar surfaces were used without treatment at the study site.

As can be seen from table 4, field tests showed the biocidal effect of the antiseptic coatings of the samples of example 1, which lasts for 4 months for fungi / yeast and more than 5 months for bacteria under conditions of regular wet cleaning of the treated surfaces.

Example 2-7 (according to the invention). The sample was prepared analogously to example 1 with a ratio of components, wt.%, Indicated in table A.

The obtained samples were tested by the methods described in example 1. The obtained properties of the compositions in examples 2-7 coincide with the properties of the sample in example 1.

The compositions according to the invention were tested for processing plastered surfaces, concrete surfaces and cement joints with grout by brushing with a flow rate of 1 liter of the composition according to example No. 1 on 20 m ² surface. A colorless hydrophobic film forms on the treated surface, the plaster does not swell and does not change the appearance. The concrete and cement surfaces do not change their operational properties. Operating conditions - daily double wet treatment of the surface covered with a disinfectant coating (plaster and cement joints of ceramic tiles), increased humidity of the concrete surface of the basement. Studies have shown that the bactericidal activity of the coating lasted for at least 3 months.

The compositions according to the invention were tested for processing cells and stalls of animals, tables for the packaging of dry feed (protein) in the conditions of daily double wet processing. As tests have shown, surface treatment of the claimed composition provides antimicrobial protection for at least 3 weeks, is environmentally friendly.

The use of the claimed composition allows to obtain a bactericidal coating in the form of varnish, which, in addition to a prolonged disinfecting effect, provides water resistance, environmental safety and the possibility of use for treating porous surfaces.

Claims (4)

1. A composition for producing an antimicrobial coating, comprising nanosized particles of an inorganic substance, an active substance, a binder and a solvent, characterized in that it contains silicon dioxide as an inorganic substance, contains a mixture of a quaternary ammonium compound and chlorhexidine as an active substance, and contains a mixture as a solvent ethyl cellosolve and butyl cellosolve, and as a binder contains a mixture of polymethylphenylsiloxane resin and a copolymer of butyl methacrylate and methyl methacrylate In the following ratio of components, wt.%:
copolymer of butyl methacrylate and methyl methacrylate 1.7-10.0 polymethylphenylsiloxane resin 5.0-20.0 silica 0.5-3.0 chlorhexidine (aqueous 20%) 3.0-8.0 quaternary ammonium compound 0.5-3.0 ethyl cellosolve 20.0-50.0 butyl cellosolve rest 2. The composition according to claim 1, characterized in that as a quaternary ammonium compound contains a salt of the General formula:
$${\text{[RR}}^{\text{one}}{\text{N}}^{+}{\text{R}}^{\text{2}}{\text{R}}^{\text{3}}{\text{] X}}^{\text{-}}\text{, (one)}$$

where R, R ¹ , R ² , R ³ are organic substituents:
methyl-; benzyl or alkyl C ₁₀ -C ₁₈ ;
X is chloride or bromide. 3. The composition according to claim 1, characterized in that as a quaternary ammonium compound contains a salt of the General formula:
$${\text{[RR}}^{\text{one}}{\text{N}}^{+}{\text{R}}^{\text{2}}{\text{R}}^{\text{3}}{\text{] X}}^{\text{-}}\text{, (one)}$$

where R, R ¹ , R ² , R ³ are organic substituents:
methyl-; benzyl or alkyl C ₁₀ -C ₁₈ ;
X is chloride or bromide,
in the form of a clathrate with urea. 4. The composition according to claim 1, characterized in that as silicon dioxide contains a hydrophilic or hydrophobic aerosil with a particle size of from 5 nm to 40 nm.