RU2194072C2 - Disinfectant-detergent - Google Patents

Abstract

FIELD: medicinal disinfection. SUBSTANCE: innovation is used for medicinal disinfection at infections of bacterial, viral and fungous etiology in establishments of different orientation (medicinal, juvenile, municipal) and in homes, and, also, could be used as a bactericide in case of petroleum yield or as a fungicide in the field of plant protection. The mentioned product contains, wt.%: salt of polyiminoimidocarbonyliminohexamethylene and acids out of group gluconic, hydrochloric, acetic, carbonic, phosphoric, 5-15; oxyethylated derivatives of polyethylene glycol, 2-15; sodium salt of ethylenediamineteraacetic acid, 0.1-1.0; and water, the balance up to 100. The innovation provides higher bactericidal, fungicidal and virulicidal activities of the product. EFFECT: improved detergent properties. 1 cl, 14 tbl

Description

 The invention relates to a disinfectant-detergent intended for medical disinfection for infections of bacterial, viral and fungal etiology in institutions of various profiles (medical, pediatric, municipal, etc.) and in everyday life, pre-sterilization cleaning of medical devices, preventive disinfection on food industry enterprises, cosmetic manufacturing facilities, for veterinary disinfection on livestock farms, and can also be used as bactericides in oil production, fungicides in the fight against plant diseases, etc.

 Known disinfectants that are widely used and containing active chlorine as an antimicrobial component (for example, chloramine B TU 6-00-1084-1-93, chlorecept TU 6-15-1691-91), oxygen (DPK TU 46-12- preparation 51-79), aldehydes (Combi disinfectant of tools and surfaces, TU RB 37332174.001-95).

 These funds are quite toxic, hazardous to the environment. Working solutions have short shelf life (except for aldehyde-containing preparations). Due to the release of significant amounts of free chlorine, oxygen or formaldehyde when surfaces and equipment are treated with such means, they deteriorate (tissues become discolored, non-metallic surfaces are degraded, metals corrode), which limits their use for the disinfection of medical instruments, surfaces of expensive diagnostic equipment, and linen. The high volatility of the components that determine the disinfecting properties of these drugs is the cause of allergic diseases of the medical staff and patients working with them. The presence of a pungent odor excludes the possibility of use in food industry enterprises. In addition, studies have shown ("Program for the fight against nosocomial infection" of the Ministry of Health of the Republic of Belarus, 1998), as a result of long-term use, pathogenic microorganisms have adapted to these disinfectants. Disinfectants themselves have become a breeding ground for pathogens and a means of spreading nosocomial infections.

 Disinfectants are known, which are a solution in water or in alcohol of various derivatives of guanidine (Chlorhexidine bigluconate; an aqueous solution of polyhexamethylene guanidine gluconate AS USSR 1687261; Polisept TU 10-09-29-89). Due to the cationic nature of their active ingredients, they not only do not have a detergent effect, but they create a hydrophobic film on the surfaces to be treated that repels water, i.e. surfaces are poorly wetted, so before disinfection with such preparations, disinfection objects must be washed with detergents. Disinfectants containing high-molecular-weight derivatives of guanidine, such as Polysept (Methodical Instructions for the Use of Polysept Disinfectants dated 12/22/1989, 15-6 / 31), are very poorly washed off with water and therefore are not applicable for the disinfection of medical instruments.

 Known disinfectant preparation (application 2695297, France). The preparation contains a mixture of calculated amounts of quaternary ammonium bases, biguanidine salts, nonionic detergents, corrosion inhibitors, stabilizers and complexing agents, for example, antiseptic additives - N- {N-2-hydroxyethyl-M-carboxyethylamidoacetate} -N, N-dimethyl-N- coco-ammonium betaine - 4.2; didecyldimethyl ammonium chloride - 10; biguanidine chloro derivatives - 4; nonionic surfactant - ethoxylated isotridecan - 7; complexing agent - ethylenediaminetetraacetic acid - 2.4; antifoam - diethanolamine oleic acid 0.5; citric acid to pH 8.3; perfumes - 0.01; dye - 0.01; the rest is water.

 Studies have shown that the drug has a narrower spectrum of action than the proposed tool (in the description of the application there is no information about its activity against fungi and viruses). It is more toxic because low molecular weight biguanidine salts are used in its composition. The disadvantages of this drug are the high cost of its constituent components, as well as the lack of their production in the CIS countries, which makes it inaccessible for widespread use.

It is known "Detergent-disinfectant" (Application BY 960436 dated 03.30.1998), containing a surfactant, antiseptic additive, complexing agent, antifoam, dye and perfume, and it contains oxyethylated polyalkylphenols as a surfactant, and in as an antiseptic additive polyhexamethylene guanidine hydrochloride in the following ratio of components, wt.%:
Oxyethylated Polyalkylphenols - 10 - 50
Polyhexamethylene guanidine hydrochloride - 5 - 20
Ethylene diamine tetraacetic acid sodium salt - 0.1 - 1.0
Carboxymethyl cellulose - 1.0 - 5.0
Dye - 0.01 - 0.5
Fragrance - 0.01 - 0.5
Water - The rest is up to 100
The main disadvantage of the detergent-disinfectant is the narrow scope of its application. A large number of surfactants (hydroxyethylated polyalkylphenols) - 10-50 - makes, in many cases, impossible to use it for machine disinfection (for example, in dairy and brewing industries) due to strong foaming, which does not even prevent the presence of antifoam. A large amount of water is required to completely remove the drug from the treated surfaces. At the same time, the washing action of solutions based on ethoxylated polyalkylphenols, at the same concentrations, is weaker than the washing effect of solutions based on surfactants, which are the subject of this application, because the first, according to the HLB system (hydrophilic-lipophilic balance), relate to wetting agents, and the second to washing agents (Surfactants. Handbook. L., 1979).

 A large number of surfactants adversely affects when it is necessary to strengthen the disinfectant activity by increasing the concentration of polyhexamethylene guanidine hydrochloride. T. about. the surfactant content also increases automatically, the so-called the effect of "swamping" and the activity of the disinfectant, instead of increasing, decreases.

Thus, the objective of the present invention is to expand the scope of use of a disinfectant-detergent:
- during medical disinfection (machine disinfection; pre-sterilization cleaning of medical devices; disinfection in foci of diseases requiring the use of increased concentrations of the drug; disinfection in neonatal wards requiring the use of toxic drugs, etc.),
- during preventive disinfection at food industry enterprises (machine disinfection; enterprises where the presence of extraneous odors is unacceptable),
- use in new areas - as a bactericide in the extraction of oil and fungicide in the fight against plant diseases.

 To solve this problem, it is necessary to enhance the washing ability, increase the bactericidal, fungicidal and virucidal activity of the product, create a range of formulations for a specific purpose, taking into account medical environmental and economic requirements.

To solve this problem, a disinfectant-detergent is proposed that contains an antimicrobial component, a nonionic surfactant, a complexing agent and water, characterized in that it contains a salt of polyiminoimidocarbonyliminohexamethylene and an acid from the group of gluconic, hydrochloric, acetic, carbonic, and as a nonionic surfactant - ethoxylated derivatives of polyethylene glycol from the group of alkyl ethers of polyethylene glycol, m polyethylene glycol onoalkylphenyl ethers, polyethylene glycol monoalkanes or block copolymers of ethylene and propylene oxides, and as a complexing agent, ethylene diamitetetraacetic acid sodium salt, in the following ratio, wt.%:
Salt of polyiminoimidocarbonyliminohexamethylene and acid from the group of gluconic, hydrochloric, acetic, carbonic, phosphoric - 5 - 15
Oxyethylated derivatives of polyethylene glycol from the group alkyl ethers of polyethylene glycol, monoalkylphenyl ethers of polyethylene glycol, polyethylene glycol monoalkanes or block copolymers of ethylene and propylene oxides - 2 - 15
Ethylene diamine tetraacetic acid sodium salt - 0.1 - 1.0
Water - The rest is up to 100
The purpose of the claimed composition is determined only by the active principle, and other components are neutral, traditionally used and are included as functional additives (dyes, perfumes, corrosion inhibitors, antifoam agents), the total amount of which does not exceed 1 wt.%. The need for their introduction is determined by consumers depending on the conditions of use of the product.

 Although the active principle of the claimed compositions is composed of well-known ingredients, they are present in unique combinations and proportions that allow achieving new technical results and advantages.

 Comparative analysis with the prototype allows us to conclude that the claimed disinfectant-detergent differs from the well-known introduction of a new antimicrobial component, namely the salt of polyiminoimidocarbonyliminohexamethylene and acid from the group of gluconic, acetic, carbonic, phosphoric, and the polyiminoimidocarbonylimino-aminomexyl acid salt of the prototype is used application with new surfactants and in other proportions.

 The set of components makes it possible to create compositions that avoid problems and solve the above problems: to fulfill the specified functions, expand the scope and use of disinfectant-detergent in more areas of the national economy, taking into account their conditions, features and specifics of sanitary, hygienic, environmental and economic requirements.

As nonionic surfactants, the product contains the following compounds or mixtures thereof:
Oxyethylated derivatives of polyethylene glycol, soluble in water, from the group of alkyl ethers of polyethylene glycol:
- monoalkyl ethers of polyethylene glycol based on primary fatty alcohols [KD6 oxanol, 0-18 oxanol, TsS-21 oxanol (TU 6-36-1029-90), OS-20 preparation (GOST 107-30-82), syntanol DT-7 , syntanol DS-10 (TU 6-14-577-77), syntanol ALM-10 (TU 6-14-864-88), syntanol ACSE-12 (TU 6-14-19-473-83)] - in surfactant-1 formulation,
- monoalkyl ethers of polyethylene glycol based on secondary fatty alcohols [neonol B 1020-12 (TU 38-40-823-79)] - in the formulation of surfactant-2,
- monoalkylphenyl ethers of polyethylene glycol [OP-7, OP-10 (GOST 8433-81), neonol AF9-10, neonol AF9-12 (TU 38.507-63-300-93)] - in the formulation PAV-3,
- polyethylene glycol monoalkanates - ethoxylated fatty acids [laurox-9 (TU 6-14-882-78), stearox 920 (TU 6-3600203335-82-92) ricinox-80] - in the formulation PAV-4,
- or block copolymers of ethylene and propylene oxides [hydropol-200, proxanol-146, proxanol-186 (TU 6-36-1029-90)] - in the formulation of surfactant-5.

Salts of polyiminoimidocarbonyliminohexamethylene and acids from the group: gluconic, hydrochloric, acetic, carbonic, phosphoric (antimicrobial components) are characterized by the following properties:
the lowest bactericidal, fungicidal and virucidal activity of carbonate, the highest fungicidal - of phosphate, virucidal - of phosphate and gluconate. Chloride and acetate are intermediate;
toxicity increases in the series gluconate, phosphate, carbonate, acetate, chloride (LD ₅₀ decreases from 2700 to 930 mg / kg);
corrosion activity increases in the series carbonate, gluconate, acetate, phosphate, chloride;
solubility in water increases in the series gluconate, carbonate, acetate, phosphate, chloride;
the cost increases in the series carbonate, chloride, acetate, phosphate, gluconate (from 2 to 50 $ / kg).

 In the CIS, only chloride is serially produced, in the far abroad - carbonate and acetate. Phosphate and gluconate are obtained in laboratories.

 The sodium salt of ethylenediaminetetraacetic acid (Trilon B), being a complexing agent, provides a good detergent ability of the agent in water of any hardness, and also, being an antioxidant, increases the stability of the agent over time. The minimum amount is calculated in such a way as to bind divalent metal ions in water, corresponding to GOST 2874-74, the maximum - to ensure the stability of the product during the expiration date.

 To reduce the number of formulations subject to expensive microbiological and virological studies, tests have been conducted of the effect of the composition of the surfactants of the claimed groups on the bactericidal activity of the proposed funds. The data are given in table. 1. The studies were conducted quantitative suspension method described below (table. 8).

 As the data in table. 1, the composition of the surfactant of the claimed groups does not affect the antimicrobial properties. Therefore, it is correct to conduct further research not on each of these surfactants, but only on one chosen arbitrarily in each study.

 The formulations of the tested funds are given in table. 2-6.

Formulation 36 - prototype composition, wt.%:
Oxyethylated Polyalkylphenols - 30
Polyhexamethylene guanidine hydrochloride - 10
Ethylene diamine tetraacetic acid sodium salt - 0.2
Carboxymethyl cellulose - 3
Dye - 0.01
Fragrance - 0,01
Water - The rest is up to 100
Disinfectant-detergent is prepared, for example, as follows.

 To prepare 1 kg of the product, 577.8 g of water is poured into a container with a capacity of 1.5 l and monoalkyl phenols based on ethylene ethylene propylene trimers are sequentially dissolved in it, for example, according to TU 38-507-63-171-91 (321 g), Trilon B , for example, GOST 10652-73 (1 g), a salt of polyiminoimidocarbonyliminohexamethylene and phosphoric acid, for example, TU 2499-001-00480135-95 (100 g), and, if necessary, a dye, for example, food green company Drakoga (0 , 1 g) and perfume, for example, cosmetic citrus directions (0.1 g).

 To compare the virucidal properties of drugs with different formulations and with the prototype, the FPV / Rostock influenza virus (H7N1) was used.

Tests were performed by the suspension method. Equal volumes of disinfectant and whole virus were combined and kept at room temperature for a predetermined time. Then, residual virus infectivity was determined by the standard method of plaques under agar coating. Monolayer cell cultures of chicken embryo fibroblast cells (FEC) were washed from growth medium with 199 medium (Sigma). After this, dilutions of the original virus-containing material were applied on the same medium. After 1 hour of contacting the dilution of the virus with cells in a thermostat at 37 ^° C, the liquid from the FEC vials was removed and a coating consisting of 2-fold concentrate of 199 medium, 1% agarose melt (Bio-Rad Laboratories) in bidistilled water, 0.005% neutral red (Sigma), benzylpennicillin (200 IU / ml, Sigma) at a temperature of 42 ^o C. After the coating has hardened, the vials were placed in a thermostat for 36 hours and then the number of plaques formed as a result of the virus multiplication and visible to the naked eye due to the presence in a dense nutrient by rytii vital dye. The test results are presented in table. 7.

 As can be seen from the table. 7, the prototype (36) has a lower virucidal activity than the samples of the claimed drug. Lower activity of the drug is also observed in cases where the content of the components is beyond the scope of the claimed (1, 14, 33). Sample 6 has good activity, but poorly washed off (see table. 10).

 When comparing bactericidal activity, typical bacterial strains were used as test cultures: E. Coli ATCC 11229; fungicidal - Candida albicans ATCC 10231. The determination of the antibacterial activity of the preparations was carried out by a quantitative suspension method.

The 24-hour agar culture of the test microbes was washed off with a 0.5% sodium chloride solution, standardized to 10 ⁹ CFU / ml. A suspension of bacteria was mixed with a disinfectant solution, after 5-15-30-60 minutes the latter was neutralized. Dilutions were prepared and plated on plates with culture media. After incubation in an incubator for 48 hours at 37 ^{° C., the} number of colonies on plates in the experiment and control was calculated. The number of surviving bacteria was calculated, decimal logarithms and reduction factors (RF) of the number of bacteria in the experiment compared with the control were determined. The results of comparing the bactericidal activity of the studied drugs are presented in table. 8, fungicidal activity in the table. 9.

 As can be seen from the table. 8 and 9, the bactericidal and fungicidal properties of the samples of the product with the content of components in the claimed range (2, 3, 10, 11, 16, 18, 23, 24, 31, 32) are higher than that of the prototype (36) and samples with increased (7, 12, 35, 13, 15, 28) or reduced (8, 13, 15, 20, 27, 29) content of components.

 Assessment of the washing ability of the proposed drugs and the prototype was carried out by the presence of blood residues according to the MU "Quality control of pre-sterilization cleaning of medical devices using reagent azopyram" 28-6 / 13.

 The washability of preparations from medical devices was compared using the eosin indicator, which selectively changes color from yellow to pink in the presence of guanidine groups of salts of polyiminoimidocarbonyliminohexamethylene.

 The studies were carried out on glass test objects, which were used glass syringes. The batch consisted of 10 disassembled syringes.

 A 20% human serum solution was prepared. The studied test objects were placed in it for 30 min, then removed, dried for 30 min on a napkin and placed in the test solution of the drug.

The concentration of the drug is 1%, the soaking time is 30 minutes. Soaking temperature 20 ^o C.

 After soaking, the test objects were washed in the same solution with a brush for 1-6 minutes and rinsed with running water for 10-300 seconds.

 Upon completion of the pre-sterilization cleaning process, the test objects were washed once again with 20 ml of distilled water, and the presence of residual amounts of polyhexamethylene guanidine salts was determined by reaction with eosin.

 The test objects were dried on a clean glass surface and the presence of latent blood was determined by the azopyram test as follows.

 3-4 drops of the working solution were poured into syringes and several times advanced with a piston in order to moisten the inner surface of the syringe with a reagent, especially the junction of glass with metal, where blood often remains. Reagents in the syringe were left for 0.5-1 min, and then drained.

 The results of studies of the washability of the preparations are given in table. 10.

 The results of studies on the presence of blood components are given in table. eleven.

 "+" - a positive test on at least one test object from the batch; "-" is a negative test on all test objects.

 As can be seen from the table. 10 and 11, only products with formulations corresponding to the claimed combine good cleaning properties and good washability from disinfected surfaces.

 The effect of the proposed drugs on sulfate-reducing (SBA) bacteria makes it possible to use them to reduce the microbiological contamination of oilfield waters.

The degree of suppression of SVB was determined in accordance with RD 39-3-973-83 "Methodology for controlling the microbiological contamination of oilfield waters and assessing the protective and bactericidal action of reagents." In studies, an accumulative culture of bacteria isolated from oilfield media was used. The results are shown in table. 12. The dosage of the funds is 50 g / m ³ .

 From the table. 12 shows that the prototype has very low activity against sulfate-reducing bacteria. Worse activity and funds, the content of components in which is beyond the scope of the claimed.

 From the data given in the description, it can be seen that the claimed agent in combinations defined by the claims has high bactericidal as well as fungicidal and virucidal properties, good detergency and good washability. Depending on the need, you can choose the most suitable one from the proposed set of recipes for one purpose or another. For example, for the disinfection of instruments combined with pre-sterilization cleaning, - the formulation with the highest surfactant content, for treating crops from diseases - with the cheapest antimicrobial component with fungicidal properties and the lowest surfactant content, for processing cuvettes for nursing premature infants - with the least toxic antimicrobial component. For processing equipment in the brewing industry, where extraneous odors are not allowed, a fragrance-free recipe. For medical institutions - each drug with a different formulation and, accordingly, for different purposes, is painted in its own color. The surfactant is selected depending on the need for detergent properties, the tendency to foaming and price.

 From the table. 7-9 and 12 shows that the ratio of active active substance to surfactant in the composition of the formulations has a great effect on the antimicrobial activity of the drug. Salts of polyiminoimidocarbonyliminohexamethylene are cationic surfactants, i.e. possess hydrophobic properties. Their solution in water does not spread over the treated surfaces, but collects in droplets and rolls, as a result of which the short-term and long molecules of the antimicrobial component do not have time to penetrate the microorganism through the cell membrane into the surface of the treated objects and the microorganisms on them. And even those molecules that remain on the surface lose their activity due to the lack of water. Accordingly, the disinfecting activity of solutions of cationic surfactants in water is low. It is necessary to change the properties of the solution so that it moistens the surface and, thus, the access of the antimicrobial component to the microorganism is facilitated. The best wetting properties of anionic surfactants, however, cationic surfactants react with them with the formation of compounds having, in the best case, static rather than cidal activity. Ampholytic surfactants also behave. Of the more than 1000 surfactants listed in the handbook (Surfactants. Handbook. L., 1979), only those in the application give the solutions the necessary wetting ability, and not only do not reduce, but very significantly (by an order of magnitude) enhance their disinfecting properties , which is confirmed by the data table. 13. Recipe 37 - a solution of a salt of polyiminoimidocarbonyliminohexamethylene in water.

 As can be seen from the table. 13, the bactericidal and fungicidal activity of preparations containing an antimicrobial component and the claimed surfactants (30 and 32) is higher than that of a solution of the same component in water (37). Because the claimed surfactants themselves do not have antimicrobial activity, we can conclude that there is a synergistic effect - the increase in antimicrobial properties is almost 10 times when mixing the active and inactive components.

 However, the ability to enhance antimicrobial ability is manifested in a relatively narrow range of ratios between the concentrations of the antimicrobial component and surfactant 1: 0.1-3. With a lower content of surfactants, solutions lose their ability to wet the surface. At higher - surfactant acts similarly to protein load - reduces the activity of the drug. The activity of the agent decreases with an absolute increase in the number of surfactants, for example, when it is necessary to use working solutions with high concentrations. In such cases, in practice, it is necessary to use those formulations of the claimed funds that contain a greater amount of antimicrobial components and less surfactant.

The effect of the surfactant content on the fungicidal activity of the agent against potato late blight pathogen is given in table. 14. The funds were used in concentrations of 1 and 4%. The tubers were kept at 20 ^° C and a relative humidity of 90-95% for a day to activate their activity, then they inflicted mechanical damage. Injured tubers were treated with working solutions of the preparation and, after drying, were infected by abundant spraying with a Ph suspension. infestans. (1x10 colonies in 1 ml), after which they were stored at 20 ^o C and a relative humidity of 70-80%. Accounting for the development of the disease was carried out 20 days after inoculation.

 Thus, a change in the content of components beyond the claimed limits leads to a deterioration in the characteristics of the tool.

 The form of application of the agent is in the form of a working solution, which is prepared by diluting the agent with water in ratios from 1: 1000 to 1:25, depending on the etiology of the pathogens of the infections to be destroyed.

 The claimed composition of the disinfectant-detergent passes toxico-hygienic tests and is preparing for industrial use.

Claims (1)

1. A disinfectant-detergent containing an antimicrobial component, a nonionic surfactant, a complexing agent and water, characterized in that as an antimicrobial component it contains a salt of polyiminoimidocarbonyliminohexamethylene and an acid from the group of gluconic, hydrochloric, acetic, carbonic, non-phosphoric surfactant - an ethoxylated derivative of polyethylene glycol from the group of alkyl ethers of polyethylene glycol, monoalkylphenyl ethers of polyethylene glycol, p monoalkanaty glycol or block copolymers of ethylene oxide and propylene oxide, and as a complexing agent - the sodium salt of ethylenediaminetetraacetic acid in the following ratio, wt. %:
Salt of polyiminoimidocarbonyliminohexamethylene and acid from the group of gluconic, hydrochloric, acetic, carbonic, phosphoric - 5-15
Oxyethylated derivatives of polyethylene glycol from the group alkyl ethers of polyethylene glycol, monoalkylphenyl ethers of polyethylene glycol, polyethylene glycol monoalkanes or block copolymers of ethylene and propylene oxides - 2-15
Ethylene diamine tetraacetic acid sodium salt - 0.1 -1.0
Water - The rest is up to 100
2. The tool according to p. 1, characterized in that it contains an antimicrobial component and a nonionic surfactant in a mass ratio of 1: 0.1-3.0.

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