RU2796846C1 - Antiseptic and disinfectant - Google Patents

Abstract

FIELD: sanitation.

SUBSTANCE: invention can be used for disinfection of various surfaces and objects, in particular for the disinfection of premises, equipment, tools, instruments, utensils, soil and other objects. Proposed antiseptic and disinfectant, including 1,6,3,8-dimethano-1,6-diaza-3,8-diazoniumcyclodecane sodium dicarbonate as an active substance.

EFFECT: agent has bactericidal and virucidal activity, is safe for humans and animals and has a prolonged antiseptic effect.

1 cl, 4 tbl, 8 ex

Description

The invention relates to the field of sanitation, medicine, veterinary medicine, pharmaceuticals, food industry.

Protection against pathogens is literally in our hands. To do this, you need to choose and use the right antiseptic. In the modern world, diseases caused by the spread of pathogenic microorganisms are widespread. Therefore, the task is to prevent the spread of infection by antiseptic treatment. According to the WHO, hand hygiene is the most effective way to reduce the spread of infections. Skin antiseptics are disinfectants designed to quickly disinfect the skin. A wide spectrum of antimicrobial action is a mandatory requirement for skin antiseptics, that is, these agents must be effective against most types of bacteria. For example, disinfection of the hands of medical staff, as well as areas of the skin of the operating and injection fields of patients in medical institutions (HCIs), is one of the important measures in the prevention of nosocomial infections. Therefore, the use of skin antiseptics in healthcare facilities is receiving increasing attention, as they have actually become more widely used in everyday medical practice.

The need for disinfection exists in many industries.

For example, modern intensive animal husbandry and poultry farming pose a potential health risk to both animals and poultry, and people working on farms (poultry farms), and air pollution reduces the quality of life of the population of nearby areas. Disinfection methods should be used as an obligatory element of production technologies. When studying the species composition of microflora in enclosures for young cattle, pathogenic strains of Staphylococcus aureus, Streptococcus faecalis, Escherichia coli, Candida spp., Aspergillus spp. (V.Yu. Morozov et al., 2016).

Disinfection is also needed in medical institutions. Disinfection involves the destruction of opportunistic and pathogenic microorganisms on all surfaces in the room, including the processing of door handles, floors, walls, window sills, switches, furniture, surfaces of doctors' equipment, air, dishes, linen. In addition, all consumables must undergo disinfection. materials, tools that are used in the work of specialists.

The main task of disinfection is the elimination, as well as the prevention of the accumulation process, the further spread of all pathogens. Disinfection is carried out, both focal and preventive. Preventive provides for the protection of people from infection, in medical institutions it is performed as a cleaning. As for focal disinfection, this procedure is performed in case of an infectious disease.

Most of the known disinfectants are mixed detergents that are used in the disinfection of various objects. As a rule, such funds cannot be used for a long time, more than four months, because addiction occurs. Almost all disinfectants contain surface-active substances (surfactants), fragrances, quaternary amine compounds (QAC), belong to the 3rd class of toxicity (hazard), do not have a long-term effect, require rinsing with water.

In addition, in many disinfectants, the active ingredient is aggressive toxic gases such as chlorine, formaldehyde, atomic oxygen, etc., which can create explosive mixtures, destroy polymeric materials, and lead to diseases and poisoning of animals and people. This makes it dangerous and practically impossible to carry out disinfection in the presence of people and animals. Solutions of many disinfectants are electrolytes that cause corrosion of metal surfaces, assemblies, their parts and assemblies.

Known means for disinfection and sterilization containing glutaraldehyde, bicarbonate and sodium hydrogen phosphate, characterized in that it additionally contains the indicator nitrazine yellow (RF patent No. 2036664).

Known disinfectant solution of sodium hypochlorite, having a pH between 10.1 and 10.7 and containing from 0.021 to 5.76% (w/v) sodium hypochlorite, characterized in that it does not contain buffers and contains no more than 2% chlorate sodium relative to the indicated amount of sodium hypochlorite (patent EA 7541)

Known antiseptic agent "AHDEZ 3000", containing as active antimicrobial substances ethyl alcohol - 75.0-83.06 wt. % and chlorhexidine bigluconate - 0.4-0.6 wt. %, as well as glycerin, castor oil, fragrance and water, (RF patent No. 2230575). The disadvantage is the appearance of irritation with prolonged use.

Known antiseptic agent "Lizanin OP", containing as active substances ethyl alcohol - 77.0-81.0% and alkyldimethylbenzylammonium chloride - 0.08-0.12%, and as functional additives - glycerin and castor oil, (patent RF No. 2113862). Such a tool has the same drawback as the tool described in the patent of the Russian Federation No. 2230575, namely, itching and peeling appear with prolonged use.

A disinfectant is known for quick and effective disinfection of surfaces, as well as for air purification and deodorization in household premises and the general living environment, which has a pleasant aroma, the main components of which are ethyl alcohol, benzalkonium chloride, a perfume composition and a hydrocarbon propellant. (RF patent No. 2679603). The disadvantage of this tool is the irritant effect and insufficient safety for the treatment of the skin.

A disinfectant is known, which is 1,6,3,8-dimethano-1,3,6,8-tetraazacyclodecane (RF patent No. 2273495). Its toxicity and alkaline reaction prevent it from being used as an antiseptic.

Thus, the known means have a number of disadvantages, and there is a need to develop effective disinfectants and antiseptics.

The invention is an antiseptic and disinfectant based on 1,6,3,8-dimethano-1,6-diaza-3,8-diazoniumcyclodecane sodium dicarbonate.

The inventive agent has disinfectant properties against viruses, bacteria, fungi and protozoa and can be used for disinfection of premises, equipment, tools, instruments, utensils, soil and other objects, has a physiological pH.

It can be used in residential and utility rooms, industrial, technological and storage facilities, in medical and research institutions, food processing plants, livestock farms and in any other place where reliable, safe and long-term disinfection is required.

Disinfection can be carried out by any method - irrigation, immersion, watering, spraying, including in the presence of animals and people, since the proposed product is safe for animals and people.

Thus, the objective of the present invention is to develop a universal and effective antiseptic and disinfectant that has a long-term effect and is safe for humans and animals.

The problem is solved by creating an antiseptic and disinfectant that has a long-term effect and is safe for humans and animals, based on 1,6,3,8-dimethano-1,6-diaza-3,8-diazoniumcyclodecane sodium dicarbonate.

The technical result of the present invention is the high efficiency of the disinfectant and antiseptic agent in the presence of a bactericidal and virucidal action, as well as its safety and long-term effect.

The invention is carried out as follows.

The active ingredient of the agent is 1,6,3,8-dimethano-1,6-diaza-3,8-diazoniumcyclodecane sodium dicarbonate.

1,6,3,8-dimethano-1,6-diaza-3,8-diazoniumcyclodecane sodium dicarbonate has a bactericidal and virucidal effect in the complete absence of toxicity and is characterized by the presence of physiological pH, which allows the use of the agent without risk to humans, animals or plants suppress the microorganisms present in it.

Disinfection with an aqueous solution of 1,6,3,8-dimethano-1,6-diaza-3,8-diazoniumcyclodecane sodium dibicarbonate provides the following: no toxicity to humans, animals and plants, no unpleasant odor and no irritant effect on the skin and mucous membranes , anti-corrosion properties and lack of aggressive action on paints and varnishes and synthetic polymeric materials and coatings, solubility in water and stability in aqueous solutions in a wide temperature range, pronounced bactericidal and virucidal action in the temperature range from 0 degrees C to +80 degrees C, the possibility of disinfection in the presence of animals and people.

The synthesis of 1,6,3,8-dimethano-1,6-diaza-3,8-diazoniumcyclodecane sodium dicarbonate is carried out from N,N'-di(chloromethyl)1,2-diaminoethane by mixing solutions of N,N'-di(chloromethyl )1,2-diaminoethane and sodium bicarbonate in equivalent ratios. It can also be carried out from 1,6,3,8-dimethano-1,3,6,8-tetraazacyclodecane by mixing 1M solutions of 1,6,3,8-dimethano-1,3,6,8-tetraazacyclodecane and sodium bicarbonate in equivalent ratios.

Elemental analysis on the CNHS analyzer "Carlo Erball08" obtained the following results

The sublimation temperature is about 165 degrees Celsius at 760 mm Hg.

1,6,3,8-dimethano-1,6-diaza-3,8-diazoniumcyclodecane sodium dicarbonate has the following structural formula:

The chemical name is 1,6,3,8-dimethano-1,6-diaza-3,8-diazoniumcyclodecane sodium dicarbonate.

Empirical formula - N ₄ C ₁₀ H ₁₈ O ₆ Na ₂

Molecular weight - 304 c.u.

Physical state - yellow crystals, soluble in water, partially sublimated at atmospheric pressure at temperatures above 165 degrees Celsius at 760 mm Hg.

Conducted studies on the activity of the proposed disinfectant and antiseptic.

All studies were carried out according to the methods given by the Federal Center for Hygiene and Epidemiology of Rospotrebnadzor “Methods of laboratory research and testing of medical prophylactic disinfectants to assess their effectiveness and safety: Guidelines. - M.: Federal Center for Hygiene and Epidemiology of Rospotrebnadzor, 2010. - 615 p.

Example 1

A plastic surface was used as test surfaces. S. aureus, E, coli, S. typhimurium, P. aeruginosa were used as test microorganisms.

Before contamination with the test culture, the surfaces were subjected to mechanical cleaning - washed with soap and water and a brush. The dried surfaces were placed horizontally, and a suspension of test microorganisms was applied to them with a pipette at the rate of 0.5 ml of 2 billion microbial suspension per area of 100 cm ² and evenly distributed over the surface with a glass spatula. The surfaces are dried at a temperature of 20 degrees C and a relative air humidity of 60%, then treated with the inventive disinfectant solution. The solution was applied by spraying at a rate of 30 ml/ ² m. The processing time was from 20 to 50 minutes.

The effectiveness of disinfection of test surfaces was monitored. The efficiency criterion is 99.9%.

After certain exposures, the surface was wiped with sterile napkins (5×5), which were then immersed in sterile water, washed, washed, and inoculated into Petri dishes with MPA. Petri dishes with crops were placed for 24-48 hours in a thermostat at 37 degrees C. The results were calculated and the percentage of disinfection was determined.

Table 1 shows that treatment with a disinfectant provides disinfection from 99.99% to 100% with an exposure of 20-50 minutes.

Example 2

Washouts were carried out for sterility in boxes in which animals were kept, namely, cattle. First, washings were carried out from the walls and floor of the boxes in which the animals were kept. Then the walls and floors of the boxes were processed. Processing was carried out once the claimed drug at a flow rate of 0.1 l/m ² . The exposure time was 20-40 minutes.

When studying the initial species composition of microflora in boxes for young cattle, pathogenic strains of Staphylococcus aureus, Streptococcus faecalis, Aspergillus spp.

Conducted control of the effectiveness of disinfection analogously to example 1. The efficiency criterion is 99.9%.

After treatment with the drug, the destruction of pathogenic strains took place, which is confirmed by the data in Table 2.

Table 2 shows that treatment with a disinfectant provides disinfection from 99.99% to 100% with an exposure of 20-40 minutes.

Example 3

A study was made of the effectiveness of the proposed composition in relation to the general microflora of the skin of the hands. From the control hand, prior to treatment with the composition, a wash was done with a sterile gauze cloth moistened with a sterile neutralizer solution. Then both hands were treated with the composition, after which the test hand was washed with a sterile gauze pad 5 × 5 cm in size, moistened with a sterile neutralizer solution. Gauze napkins were placed in separate wide-mouthed test tubes with glass beads and 10 ml of sterile saline and washed for 10 minutes. Then the washing liquid was added in 0.5 ml to a Petri dish and filled with casein agar, 0.2 ml in Endo medium and yolk-salt agar. The cultures were incubated in a thermostat at 37°C for 48 h, after which the grown colonies were counted. The criterion for the effectiveness of an antiseptic is a decrease in the total microbial contamination of the skin by at least 95%.

According to the data obtained, the resulting composition is an effective antiseptic for the treatment of hand skin.

Example 4

The prolonged antimicrobial action of the antiseptic is evaluated on the hands of the testers in relation to the general microflora of the skin. The hands of the testers are treated with a skin antiseptic for 30 s - 1 min. Then, from one control hand, each tester is flushed with a sterile gauze napkin moistened with a sterile neutralizer solution, after which the testers perform work at their workplace, but during the entire experiment (from 30 minutes to 3 hours) they do not wash their hands with water and toilet soap. Washes from the other experimental hand are made with a sterile gauze soaked in a sterile neutralizer solution every hour from the start of the experiment. Washouts are done every hour by different testers. After taking swabs, gauze napkins are placed in separate wide-mouth tubes with sterile saline (10 ml each) and glass beads, shaken for 10 minutes. Then the washing fluid is inoculated from the experimental and control tubes onto casein agar. The crops are incubated in a thermostat at 37°C for 48 hours, after which the grown colonies are counted. If the skin antiseptic has a prolonged antimicrobial effect, then for several hours after hand treatment with an antiseptic, the number of microorganisms found in the washouts remains minimal (compared to the amount that is detected immediately after hand treatment with an antiseptic).

The analysis carried out according to the presented method showed the following.

10 testers took part in the experiment. At the same time, the tester performed various work (work with papers, work on the conveyor, packing products in the workshop).

The table shows that the agent according to the invention has a prolonged antiseptic effect.

In addition, experiments conducted to determine the duration of action of the agent showed that the drug retains pronounced properties in aqueous solutions for at least 180 days, which was the period of observation of the drug.

Example 5

Studied the local irritating effect of the proposed agent. The agent was applied once to the skin of guinea pigs for 2 weeks at a dose of 2 ml/kg of animal weight without subsequent rinsing with water. The study showed that the application of the agent did not cause damage to the skin, edema, the skin temperature in the control area was 37.2±0.2°C and in the experimental area - 37.3±0.2°C). As a result of the experiments, no irritating effect of the drug on the skin was revealed.

Example 6

The authors of the present invention also carried out experiments to evaluate the sensitizing effect of the antiseptic composition for disinfecting the skin in mice using a "delayed action" hypersensitivity reaction (GHR). Studies testified to the absence of a pronounced sensitized effect of the agent.

The drug belongs to the 4th hazard class: low-hazard substances.

Example 7

1,6,3,8-dimethano-1,6-diaza-3,8-diazoniumcyclodecane sodium dicarbonate has a pronounced virucidal effect. A concentration of 0.1% leads to a decrease in the titer of SARS-CoV-2 viruses by 10,000 times within an hour.

In a toxicity study, the LD ₅₀ (dose at which 50% of mice die) was found to be slightly over 12,000 mg per kg of body weight in mice when administered orally.

However, for comparison:

LD ₅₀ salt - 3000 mg / kg,

LD ₅₀ food ethyl alcohol - 2080 mg / kg,

LD ₅₀ caffeine - 192 mg / kg,

LD ₅₀ 1,6,3,8-dimethano-1,3,6,8-tetraazacyclodecane - 2090 mg/ml.

Thus, the presented data confirm the effective virucidal effect of the drug.

Comparative Example 8

The antibacterial score of 1,6,3,8-dimethano-1,6-diaza-3,8-diazoniumcyclodecane sodium dicarbonate was compared with the antibacterial score of 1,6,3,8-dimethano-1,3,6,8-tetraazacyclodecane ( patent of the Russian Federation No. 2273495).

For this, the experiment was carried out as follows.

Antibacterial evaluation was studied with the causative agents of botulism (Clostridium botulinum), colibacillosis (E. coli) and salmonellosis (Salmonella enteridis).

The minimum bactericidal concentration (MBC) was determined from the results of comparative titration of bacteria samples by the method of serial dilutions in meat-peptone broth (MPB) followed by seeding on meat-peptone agar (MPA).

The study showed that 1,6,3,8-dimethano-1,6-diaza-3,8-diazoniumcyclodecane sodium dicarbonate at a concentration of 0.5% (0.5 mg / ml) inactivates the causative agents of botulism (Clostridium botulinum) for 24 hours ), colibacillosis (E. coli) and salmonellosis (Salmonella enteridis).

Experiments with 1,6,3,8-dimethano-1,3,6,8-tetraazacyclodecane show 4-10 times lower efficiency in relation to the same microorganisms.

Thus, the above experimental data show that the claimed agent is an effective antiseptic and disinfectant, has bactericidal and virucidal activity, is safe for humans and animals, and has a prolonged antiseptic effect.

Claims (1)

An antiseptic and disinfectant containing 1,6,3,8-dimethano-1,6-diaza-3,8-diazoniumcyclodecane sodium dicarbonate as an active substance.