RU2395962C1 - Disinfectant - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: invention refers to medical and veterinary microbiology and biotechnology and can be used for making preparations for indoor surface disinfection, sanitary fittings and biotechnology equipment, and items of care. The disinfectant contains alkyldimethylbenzylammonium chloride, hydrogen peroxide, ethanol, glutaraldehyde, sulfonic, perfluordecahydronaphthalene and water in a certain ratio. ^ EFFECT: invention provides high microbiocide activity with respect to a wide range of vegetative and cryptogamous forms of microorganisms with rather low concentration of a process solution, maintains its properties for two years of storage, resist the action of external factors. ^ 7 tbl

Description

The present invention relates to sanitary ecology and disinfection and can be used in the biotechnological, food, medical, veterinary, processing industries and, primarily, to obtain preparations for the disinfection of surfaces in rooms, medical, veterinary and biotechnological equipment, and patient care items.

Disinfectants are known, such as Deconex 50 FF, Lysafin, Catamine AB, Alaminol, Sterrilium and others, which are a mixture of active components with water in a certain concentration.

Deconex 50 FF is an aqueous solution of the composition of the following composition (wt.%): Glyoxal - 12.0; glutaraldehyde - 0.5; didecyldimethylammonium chloride - 7.5; nonionic surfactant (surfactant) - 4.0; a mixture of essential oils - 1.0; water - the rest (Guidelines for the use of Deconex 50 FF for the disinfection of Borer Chemie AG (Switzerland), developed by the Research Institute of Preventive Toxicology and Disinfection of the State Committee for Sanitary and Epidemiological Surveillance of the Russian Federation. M., 1998 ").

Lysafine is a disinfectant containing an aqueous solution of the following ingredients (wt.%): Glutaraldehyde - 0.3-0.7; alkyldimethylbenzylammonium chloride - 25.0-35.0; glyoxal - 3.5-6.5; nonionic surfactant - 4.0-8.0; ethyl alcohol - 6.0-10.0; Trilon B - 0.08-0.12 (RF Patent No. 2145238. Disinfectant).

Catamine AB is a disinfectant based on an aqueous solution of 49-51 (wt.%) Alkyldimethylbenzylammonium chloride. Sterrilium is an aqueous solution of the following composition (wt.%): 2-propanol - 45.0; 1-propanol - 30.0; Quaternary ammonium compound 0.2. Alaminol is an aqueous solution of the composition of the following composition (wt.%): Catamine AB-5, glyoxal - 5 (Disinfectants. Part 1. Disinfectants. Handbook. Issue 2. - M., 1998 - P.72-153 )

These funds are not effective against spore-forming microorganisms, have high concentrations of working solutions, long exposure times.

The closest is a disinfectant of the following composition, wt.%:

Alkyldimethylbenzylammonium chloride 20.0-22.5 glutaraldehyde 0.8-1.5 benzotriazole 3.0-5.0 hydrogen peroxide 5.0-10.0 monohydroxy alcohol 5.0-10.0 water rest

(RF patent №2286145. Disinfectant).

The use of the above agents with a wide spectrum of action is unsafe for human health, since an effective bactericidal effect is achieved at high concentrations of working solutions, which requires the observance of certain precautions. When diluting the composition, a decrease in the microbicidal (bactericidal and sporocidal) action is obvious. The disadvantages of the preparations include a relatively low efficiency against spore-forming bacteria and fungi, as well as rather long exposure times during processing.

The objective of the invention is to increase the activity of the disinfectant against spore-forming microorganisms while maintaining a wide spectrum of its action while preserving antimicrobial activity in low concentrations and increasing environmental and operational safety.

This object is achieved in that the claimed disinfectant contains alkyldimethylbenzylammonium chloride, hydrogen peroxide, ethyl alcohol, glutaraldehyde, sulfonol, perfluorodecalin and water in the following ratio, wt.%:

Alkyldimethylbenzylammonium chloride 10.0 hydrogen peroxide 5,0 ethanol 5,0 glutaraldehyde 0.5 sulfonol 0.5-2.0 perfluorodecalin 0.2-1.0 water rest

As alkyldimethylbenzylammonium chloride, Catamine AB (Russia) is used according to TU 9392-00348482528, industrially produced in the form of aqueous solutions with an active substance concentration of 50 ± 0.5%.

As the aqueous medium, distilled or demineralized or drinking water is used according to GOST 6709-72 or GOST 2874-82.

The inventive composition contains hydrogen peroxide according to GOST 10929-76, ethyl alcohol according to TU 6-09-1710-77, glutaraldehyde according to TU 8-20603.1000, sulfonol (sodium salt of alkylbenzenesulfonic acid) according to TU 2481-135-07510508-2007 and perfluorodecalin according to TU 95-1233-92.

In the inventive composition, the simultaneous use of perfluorodecalin, alkyldimethylbenzylammonium chloride, ethyl sulfonol, glutaraldehyde and hydrogen peroxide in a slightly acidic (pH 6.5-7.0) aqueous medium at the claimed ratio of the components is proposed.

Previously, disinfectant formulations were not known in which the quaternary ammonium salt, glutaraldehyde, ethyl alcohol, hydrogen peroxide, perfluorodecalin and sulfonol were simultaneously present. The simultaneous use of quaternary ammonium salt, glutaraldehyde and hydrogen peroxide with perfluorodecaline and sulfonol allows you to get an unexpectedly high increase in the microbicidal and sporocidal action of the disinfectant, having solved the problem of the invention - to increase the activity of the obtained product, reduce the concentration of working solutions, increase the environmental safety of the used solutions of the disinfectant. In addition, the claimed composition is characterized by increased phase stability, the shelf life without loss of activity is more than 2 years.

The antimicrobial activity of the claimed composition significantly exceeds the activity of currently known disinfectants, which can be explained by the mutual influence of the ingredients of the composition on each other, increased activity due to the use of perfluorodecalin microparticles, which ensures the transport of the complex of microbicidal components of the disinfectant through microbial membranes into the cell, by physicochemical mechanisms effects on living vegetative cells and spores of prokaryotes and eukaryotes of a combination of active substances and intermediate compounds containing reactive groups obtained by their interaction.

The various mechanisms of interaction of the reactive components of the proposed agent with the functional and structural components of the cells of microorganisms that manifest themselves change the bioenergetics of the cell, destructively affect the cellular structures and kinetics of ion transfer through lipophilic membranes, disrupt the permeability of membrane structures, block the work of permeases and mitochondrial “generator” of the cell, stop functioning enzymatic and electrochemical complexes provide enhanced synergistic the action of the used disinfectants and the manifestation of not only the bactericidal effects that are already known to them, but also make it possible to obtain an ultimately total effect.

The drug is a light yellow, slightly opalescent liquid in transmitted light, explosion and fireproof, belongs to hazard class IV, i.e. safe to use, does not irritate the skin with prolonged use, does not cause destruction of the treated surface, metal corrosion. The stability of the resulting composition provides the possibility of long-term storage (at least 2 years) without changing sporocidal activity.

To confirm the feasibility of the invention and to obtain the indicated technical result, a disinfectant was prepared and its microbicidal activity was tested against laboratory strains of microorganisms of the genera Bacillus, Staphylococcus, Pseudomonas, Clostridium, Aspergillus and Fusarium.

The compositions were prepared as follows. Perfluorodecalin was poured into a container containing an aqueous solution of sulfonol at a temperature of 20-25 ° C. The resulting heterogeneous mixture was subjected to a mixing procedure for 30 minutes on a high-speed mixer without air at a rotor speed of at least 4000 rpm with immersion of a rotating blade or mixer turbine in perfluorodecalin. Then, an alcoholic solution of glutaraldehyde and alkyldimethylbenzylammonium chloride was added, as well as an aqueous solution of hydrogen peroxide, and stirring was performed without air at a rotor speed of 1000 rpm.

To obtain comparative data, the compositions of the inventive disinfectant (examples No. 1-3) were prepared, are shown in table 1. In similar conditions, the compositions of control disinfectants (control examples No. 4-6) were prepared, as well as the composition according to the prototype RF patent No. 2286145 of 15.03 .2005 (example No. 8). Compounds analogous to No. 7 ("Lysofin") and prototype No. 8 were prepared in a similar way, i.e. by mixing the active substance, which is used alkyldimethylbenzylammonium chloride and glutaraldehyde in ethyl alcohol with the addition of hydrogen peroxide and a previously prepared aqueous solution of benzotriazole (only for No. 8). The formulations of the prepared compositions are shown in table 1.

Performance indicators were determined by the methods described in the "Instructions for the determination of the bactericidal properties of new disinfectants No. 739-68" and in the regulatory document approved by the Chief State Sanitary Doctor of the Russian Federation and the Chairman of the Russian State Standard, "Test methods for disinfectants to assess their safety and effectiveness" . Moscow, 1998

The bactericidal effect of the drugs was studied in concentrations of a disinfectant of 0.2%; 0.5% and 1.0% in parallel rows with an exposure of 60 min. The following media were used as nutrient media: meat peptone agar, Endo, Saburo agar media, based on hydrochloric acid hydrolyzate of casein. To determine the concentration of microorganisms, the optical turbidity standard of the production of GISK im. L.A. Tarasevich, Moscow, sterile saline. When preparing a neutralizer solution based on buffered saline, the following additives were used: 3.0% Tween-80; 5.0% skim milk; 0.1% cysteine; 0.5% sodium thiosulfate; 3.0% saponin and sterile tap water. The tests were carried out on 2 × 2 cm cambric (coarse calico) test objects without protein and with a protein load, impregnated with a suspension containing 1 cm ³ 2 · 10 ⁹ vegetative microbial cells (bacterial or fungal spores) according to the optical turbidity standard for the production of . L.A. Tarasevich. To determine the effect of protein load (organic pollution) on the level of antimicrobial activity of the disinfectant, we applied the corresponding microbial culture with 10% horse serum to the test object. The microbicidal (fungicidal, bactericidal and sporocidal) action was studied in parallel rows with an exposure of 60 minutes. As test microbes, laboratory strains of Bacillus cereus 94-1, Bacillus anthracis 55, Bacillus subtilis 5, Staphylococcus aureus 906, Pseudomonas aeruginosa 423, Clostridium septicum No. 59, Clostridium oedematiens No. 79, Clostridus niumpermolytic sporotrichiella var. poae BKMF-1606 (Tables 2-6).

Crops of samples on solid nutrient media taken after exposure to disinfectants were evaluated after 2-5 days. The results of the control of microbicidal action were recorded by the presence (+), significant inhibition or the presence of single colonies (±) or lack of growth (-).

The results of the control of bactericidal, fungicidal and sporocidal action were evaluated by the presence or absence of growth, including the dynamics in the control and experimental series. Studies have established that the claimed disinfectant has increased activity against spore and vegetative forms of microorganisms of different groups. Moreover, in relation to all groups of spore and vegetative forms, the test strains of bacteria and fungi of the claimed tool (compounds No. 1-3) are noticeably more effective in terms of microbicidal activity of the prototype.

Determining the effectiveness of disinfecting test objects from spores of anthrax microbe, clostridia and fungi with 0.5% and 1.0% solutions at an exposure of 60 minutes showed that when processing with composition No. 7 (analogue) and No. 8 (prototype) there was a continuous increase in case and inhibited growth in the second in the presence of organic pollution, while when processing with compounds No. 1-3 (the claimed agent), complete suppression of growth was observed, which indicated the death of all resistant forms of microbes even in the presence of organic pollution in the culture ( s).

Similar results were obtained in relation to vegetative bacterial cultures of Pseudomonas aeruginosa and Staphylococcus aureus when exposed to 0.2% solutions No. 1-3 (the claimed agent), complete growth inhibition was observed in the presence of crop growth after exposure to the prototype disinfectant.

The effective concentration of the working solution, in which all microbial forms of bacteria and fungi (spore and vegetative) die, i.e. there is a complete bactericidal and sporocidal effect of even organic pollution (serum), 0.5% should be recognized.

Thus, the antiseptic obtained by examples No. 1-3 has a high level of activity against various groups of microorganisms.

Control compositions of disinfectants that did not contain perfluorodecalin and sulfonol — components that cause a significant difference between the claimed disinfectant (examples No. 4-6) were significantly inferior to it in antimicrobial activity, which is especially noticeable in the analysis of control composition No. 6, in which both were absent component.

The results of the assessment of the toxicity of disinfectants when injected under the skin and in the abdominal cavity of white mice (according to K.K.Sidorov) are presented in table 7. It should be noted that the claimed compositions of the disinfectant are characterized by increased environmental and toxicological safety in comparison with the analogue and prototype. Medium-lethal (LD ₅₀ ) doses of the claimed disinfectant for subcutaneous and intraperitoneal administration to white mice exceeded 4500 and 3000 mg / kg of animal weight, respectively, which allowed the claimed agents to be classified as relatively harmless compounds or toxicity class No. 6 (according to K.K.Sidorov). The compositions according to example No. 7 (analogue) and No. 8 (prototype) containing toxic ingredients (benzotriazole) and high concentrations of alkyl dimethylbenzylammonium chloride, hydrogen peroxide, alcohol, as well as a number of other components that are not present in the inventive tool, have 3-30 times higher toxicity to animals with subcutaneous and intraperitoneal administration, although they belong to the class of low toxic substances (class 4 according to K.K. Sidorov).

Studies on the storage of the inventive disinfectant for 2 years in a plastic container under the influence of temperature in the range from 5 to 35 ° C with the subsequent evaluation of the microbicidal action made it possible to establish that the inventive preparation is resistant to external factors, preserves the properties of the freshly prepared solution throughout the entire storage time .

Thus, the claimed composition of the disinfectant allows you to ensure a high level of its microbicidal (sporocidal, bactericidal and fungicidal activity) in relation to a wide range of stable forms of microorganisms at relatively low concentrations of the working solution. The inventive composition allows to obtain an effective disinfectant related to relatively harmless compounds or toxicity class No. 6, significantly exceeding the comparable parameters (increased disinfecting activity and harmlessness) of known analogues.

Table 1 The compositions of the claimed and control disinfectants, analogue and prototype Components The content in the disinfectant, No. ..., wt.% examples of the invention control examples (analogue) prototype one 2 3 four 5 6 7 8 Perfluorodecalin 0.2 0.5 1,0 - 1,0 - - - Sulfonol 0.5 1,0 2.0 2.0 - - - - Glutaraldehyde 0.5 0.5 0.5 0.5 0.5 0.5 0.3-0.7 0.8-1.5 Hydrogen peroxide 5,0 5,0 5,0 5,0 5,0 5,0 - 5.0-10.0 Ethanol 5,0 5,0 5,0 5,0 5,0 5,0 6.0-10.0 5.0-10.0 Glyoxal - - - - - - 3,5-6,5 - Benzotriazole - - - - - - - 3.0-3.5 Nonionic surfactant - - - - - - 4.0-8.0 - Trilon B / water - - - - - - 0.08-0.12 - Alkyldimethylbenzylammonium chloride 10.0 10.0 10.0 10.0 10.0 10.0 25.0-35.0 20.0-22.5 Water 78.8 78.0 76.5 77.5 78.5 79.5 61.12-39.68 54.0-57.0 Notes: 1-3 - variants of the compositions according to the claimed invention; 4-6 - control examples without one or two of the claimed essential components in the disinfectant; 7 - lysafin; 8 - prototype - RF patent No. 2286145 dated 03/15/2005.

Table 7 The results of assessing the toxicity of disinfectants when injected under the skin and in the abdominal cavity of white mice (according to K.K.Sidorov) Disinfectant No. (composition is listed in table 1) The average lethal dose (mg / kg) for white mice with the introduction Toxicity Class toxic
STI under the skin into the abdominal cavity one > 4500 > 3000 relatively harmless 6 2 > 4500 > 3000 relatively harmless 6 3 > 4500 > 3000 relatively harmless 6 four > 4500 > 3000 relatively harmless 6 5 > 4500 > 3000 relatively harmless 6 6 > 4500 > 3000 relatively harmless 6 7 151-1500 101-1000 little toxic four 8 151-1500 101-1000 little toxic four

Claims (1)

A disinfectant containing alkyldimethylbenzylammonium chloride, hydrogen peroxide, ethyl alcohol, glutaraldehyde, sulfonol, perfluorodecalin and water in the following ratio, wt.%:
Alkyldimethylbenzylammonium chloride 10.0 hydrogen peroxide 5,0 ethanol 5,0 glutaraldehyde 0.5 sulfonol 0.5-2.0 perfluorodecalin 0.2-1.0 water rest