RU2521323C1 - Skin disinfection treatment agent - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: agent contains three active substances: polyhexamethylene guanidine hydrochloride, alkyldimethylbenzylammonium chloride and N,N-bis(3-aminopropyl)dodecylamine. The agent also contains liposentol hydro, lactic acid, a fragrance and water, with a defined amount of components in wt %.

EFFECT: agent has a wide range of disinfecting action, low toxicity and negative effect on skin.

3 tbl, 1 ex

Description

The invention relates to the field of sanitation and hygiene and can be used in everyday life for hygienic treatment of hands, feet, as well as skin integument fields, elbow bends of donors in medical institutions. It can also be used to treat the skin of the hands and feet of personnel at enterprises in the food industry, utilities, catering.

The development of chemical antiseptic methods remains an urgent problem due to the constant change in the species composition and properties of the microbial flora.

The barrier properties of the skin, which determine the body’s protection against environmental influences, are ensured by the interaction of the lipids of the stratum corneum and the water-lipid layer. In turn, the functioning of the skin barrier layer depends on the structure and composition of the intercellular lipid system.

It should be noted that the body tends to restore the violation of the barrier function of the skin by producing the main lipids contained in the skin: ceramides or ceramides, cholesterol, fatty acids, as well as phospholipids, glycosylceramides and cholesterol sulfate.

Since the skin contains many fat and protein ingredients, they create a favorable environment for the habitat of numerous microorganisms: bacteria, fungi and viruses.

To restore the barrier functions of the skin help biocidal components included in the compositions used for antiseptic treatment of the skin.

Chlorhexidine bigluconate is widely used as a biocidal component (Plivacept drug, manufacturer - Pliva company, Croatia. A. Krasilnikov. Handbook of antiseptics. - Minsk: Vysshaya shkola, 1995, p. 83).

Chlorhexidine bigluconate is used as the main active ingredient in most modern skin antiseptics. However, it is known that chlorhexidine bigluconate is weakly effective against a number of microorganisms, which limits the range of application of such compositions.

It is known to use for the treatment of hands of medical personnel, purulent wounds, injection and surgical fields of 0.5-2.0% aqueous or 0.5% aqueous-alcoholic solution of polyhexamethylene guanidine phosphate (US Pat. RF No. 2122865, class A61L 2/16, 1998 g.).

The disadvantages of this composition include the fact that polyhexamethylene guanidine phosphate (PHMG), synthesized based on guanidine carbonate, is characterized by a relatively low antimicrobial activity and is not sufficiently active against viruses, mesemary fungi and mycobacterium tuberculosis.

The closest in composition and effect achieved technical solution to the proposed invention is "Antiseptic and disinfectant" (US Pat. RF No. 2359704, CL A61L 2/18, 2009).

The product contains alkyldimethylbenzylammonium chloride, N, N-bis (3-aminopropyl) dodecylamine, polyethylene glycol-7 glycerol cocoate, d-panthenol, ethyl panthenol, nicotinic acid, ascorbic acid, hyaluronic acid, salicylic acid, glycolic acid, citric acid, citric acid 200: 1 and water in the following ratio of components in wt.%:

alkyldimethylbenzylammonium chloride 0.15-0.6 N, N-bis (3-aminopropyl) dodecylamine 0.3-1.0 polyethylene glycol-7 glycerol cocoate 0.08-0.3 d-panthenol 0.01-0.04 ethyl panthenol 0.001-0.01 a nicotinic acid 0.0005-0.02 vitamin C 0.0015-0.01 hyaluronic acid 0.0003-0.009 salicylic acid 0.001-0.01 lemon acid 0.002-0.04 glycolic acid 0.001-0.01 Aloe Vera extract 200: 1 0.02-0.1 water rest

In addition, the tool may contain in its composition liposenthol hydro in the amount of 0.08-0.3 wt.%.

However, ammonium compounds included in the well-known product: quaternary ammonium compound (QAS) - alkyldimethylbenzylammonium chloride and tertiary amine - N, N-bis (3-aminopropyl) dodecylamine are among the strong antimicrobial substances, but do not have a long-term effect (prolonged effect). In addition, certain types of the most resistant microorganisms are not suppressed by the ammonium compounds used (spore forms, tuberculosis mycobacteria), and a high content in the known composition of disinfecting components in an amount of up to 1% can have a toxic effect on the body and cause skin dermatitis.

The technical problem solved by this invention is to increase the spectrum of the disinfectant effect of the agent, reduce its toxicity and negative effects on the skin (dryness, cracks) with its frequent use and increase the prolonged effect and consumer properties (shelf life).

To achieve this goal, a tool for disinfecting treatment of the skin, including alkyl dimethylbenzylammonium chloride, N, N-bis (3-aminopropyl) dodecylamine, liposentol hydro and water, additionally contains polyhexamethylene guanidine hydrochloride, 40% lactic acid and perfume, while alkyl dimethyl benzyl used with a chain length of C ₁₂ -C ₁₆ in the following ratio of components in wt.%:

alkyldimethylbenzylammonium chloride with chain length C ₁₂ -C ₁₆ 0.08-0.12 N, N-bis (3-aminopropyl) dodecylamine 0.08-0.12 polyhexamethylene guanidine hydrochloride 0.22-0.28 liposenthol hydro 0.1-0.3 40% lactic acid 0.1-0.3 perfume 0.02-0.1 water rest

The invention is illustrated as follows.

The compound of polyguanidine - PHMG hydrochloride used in the composition for disinfecting the treatment of the skin has a wide range of biocidal activity: antibacterial, fungicidal, virucidal. It has low toxicity, does not penetrate intact skin (hazard class IV), remains on it for a long time, protecting it from environmental influences.

As a polyguanidine compound, low molecular weight (n = 30-50) PHMG hydrochloride is used.

For example, Polisept - TU 9392-001-32963622-99, or Biopag - TU 9392-008-41547288-00. The trademark "Biopag" belongs to ROOIETP.

Alkyldimethylbenzylammonium chloride is a clear, colorless to yellow liquid. This quaternary ammonium compound (QUAS) is characterized by a wide spectrum of biocidal action and has the properties of a surfactant.

The proposed skin disinfectant uses alkyldimethylbenzylammonium chloride with a chain length of C ₁₂ -C ₁₆ (TU 9392-003-48482528-99) of the following structural formula

where n = 12-16.

The use of alkyl dimethylbenzylammonium chloride with a chain length of C ₁₂ -C ₁₆ is due to the fact that among mono-quaternary ammonium salts, compounds that contain 12-16 carbon atoms in the radical, as a rule, exhibit maximum activity.

The introduction of another disinfectant component of the tertiary amine, N, N-bis (3-aminopropyl) dodecylamine, into the composition of the agent is due to the enhancement of the biocidal properties of the composition. Use the disinfecting substance “Triamine U-12D”, or “Triamine U-12D 30”, or “Lonzabak 12.100” (ND firm Akzo-Nobel, Sweden or ND firm Lonza Switzerland).

N, N-bis (3-aminopropyl) dodecylamine has a wide spectrum of antimicrobial activity against bacteria, fungi and viruses, and retains its activity in a wide range of pH values.

Currently, the mechanism of action of polyalkylene guanidines (PAGs) on microorganisms is as follows:

- guanidine polycations are adsorbed on a negatively charged surface of a bacterial cell, thereby blocking respiration, nutrition, and metabolite transport through the bacterial cell wall (this effect depends on the ionic charge of the polycation);

- PAG macromolecules diffuse through the cell wall, causing irreversible structural damage at the level of the cytoplasmic membrane, nucleotide, cytoplasm (this process depends on the magnitude of surface activity, lipophilicity, solubility in water, molecular volume of the diffusing particle);

- PAGs bind to acid phospholipids, proteins of the cytoplasmic membrane, which leads to its rupture (this effect depends on the concentration and molecular weight of the antiseptic);

- the result of this is the blockade of glycolytic enzymes of the respiratory system, the loss of pathogenic properties and the death of a microbial cell.

The combined interaction of alkyl dimethylbenzylammonium chloride (HAC), N, N-bis (3-aminopropyl) dodecylamine (tertiary amine) and PHMG hydrochloride has a stronger bactericidal effect than each of these disinfectants separately. In addition, the spectrum of antimicrobial activity is expanding significantly, and due to the formation of a molecular polymer film of polyguanidines on the treated surface, the antimicrobial action of the agent increases several times.

There is a synergistic interaction of the components with each other.

Synergism is explained by the fact that the molecules of two ammonium compounds: a quaternary ammonium and tertiary amine and a polymer guanidine compound differ in electronic structure and therefore interact chemically or electrostatically with each other, forming “zwitterionic” compounds.

The vitamin complex liposentol hydro is used in the proposed composition of the product to prevent aging of the skin and its intense nutrition. In addition, this component has a significant bactericidal effect, which significantly enhances the bactericidal effect of the main disinfecting components of the composition: PHMG hydrochloride, alkyldimethylbenzylammonium chloride and N, N-bis (3-aminopropyl) dodecylamine.

Liposentol hydro - vitamin complex containing d-panthenol, ethyl panthenol, nicotinic acid, ascorbic acid, hyaluronic acid, salicylic acid and citric acid (TU RB 101541059.007-2000).

40% lactic acid regulates the pH in the proposed composition.

Lactic acid (Lactic Acid), 2-hydroxypropionic acid is a yellowish liquid. Non toxic It is well soluble in water, glycerin, alcohol. It is formed during lactic fermentation of sugars. Use lactic acid TU 6-09-3372-75.

Lactic acid also has an anti-inflammatory effect, promotes exfoliation of the epidermis, moisturizes and dehydrated and sagging skin, eliminates small wrinkles.

Fragrance is used to give the product a pleasant smell. You can use the fragrance "Lemon Super" AGF465 // 5. It is possible that you can use perfumes with a different smell: mint, green tea, etc.

Water is used as the basis for the composition of the product according to GOST 609-84 (distilled) or purified.

The composition is prepared as follows.

PHMG hydrochloride is dissolved in a container of water and mixed thoroughly. Then, with constant stirring, alkyldimethylbenzylammonium chloride, N, N-bis (3-aminopropyl) dodecylamine, liposentol hydro, perfume, 40% lactic acid and water are added successively to this prescription amount. In this case, the pH of the composition is determined and its lactic acid is adjusted to a pH of 4.5-6.0.

Example No. 1 of a specific implementation.

alkyldimethylbenzylammonium chloride with chain length C ₁₂ -C ₁₆ 0.1 wt.% N, N-bis (3-aminopropyl) dodecylamine 0.1 wt.% polyhexamethylene guanidine hydrochloride 0.25 wt.% liposenthol hydro 0.5 wt.% 40% lactic acid 0.1 wt.% perfume "lemon super" 0.1 wt.% water rest

Other examples of specific performance are summarized in table No. 1.

The percentage of components is optimal and identified on the basis of numerous experiments.

The proof of the declared limits of the content of the components is summarized in table No. 1.

The percentage of disinfectant components is significantly lower than that of the prototype.

The toxicity and hazard testing of the proposed product was carried out at the Federal State Institution of Scientific Research Institute of Disinfectology of Rospotrebnadzor and is reflected in the Scientific Report dated 07/13/2012.

According to the report, the product has fungicidal, bactericidal, tuberculocidal and virucidal activity. It was revealed that it does not have an irritating effect on the skin, has a wound healing effect.

The proposed tool is assigned to class IV low-hazard substances.

According to the composition of the prototype tool (Pat. RF No. 23599704) contains active substances: alkyldimethylbenzylammonium chloride and N, N-bis (3-aminopropyl) dodecylamine in the aggregate from 0.45 to 1.5 wt.%.

The proposed tool contains active substances: alkyldimethylbenzylammonium chloride, N, N-bis (3-aminopropyl) dodecylamine and polyhexamethylene guanidine hydrochloride, but in the aggregate their number is much smaller - within 0.38-0.52 wt.%, Which significantly reduces the irritating skin effect and toxicological characteristics of the product while maintaining high disinfectant properties.

The study of the antimicrobial activity of the drug was carried out using the method of cambric test objects in accordance with the "Methods of laboratory research and testing of disinfectants to assess their effectiveness and safety", R 4.2.2643-10, M., 2011.

The study of the effectiveness of the product during hygienic processing of hands was carried out in accordance with the “Methods of laboratory research and testing of disinfectants to assess their effectiveness and safety”, R 4.2.2643-10, M., 2011 and the standards set forth in the collection “Regulatory safety and efficacy indicators disinfectants subject to control during mandatory certification ”No. 01-12 / 75-97.

When studying the antimicrobial activity of the agent, cambric test objects were used as test objects. As test microorganisms, Escherichia coli (E. coli strain 1257), Staphylococcus aureus (S. aureus strain 906), Pseudomonas aeruginosa (Ps. Aeruginosa strain 15), and Candida albicans fungi (strain 15) were used as test microorganisms.

When studying the virucidal activity of the drug, type 1 polio virus (vaccine strain LSc 2 ab) was used as a test microorganism. The virus was cultured in a transplanted Vero green monkey kidney cell culture. The infectious titer of the virus was 6.5 lg TCDso / ml. The final count was performed after two consecutive passages in 1 daily Vero cell culture. As a neutralizer, 80% inactivated cattle serum was used.

The antimicrobial effect was neutralized by immersion in a universal neutralizer (tween 80, histidine, cysteine, lecithin) contaminated with a suspension of the above test microorganisms of the cambric test objects, after which the test objects were placed in test tubes with nutrient media.

The effectiveness of the disinfecting effect of the product was evaluated on the hands of the testers when they were artificially seeded with a test culture (E. coli strain 1257) and in relation to the total contamination of the skin of the hands, while microbial contamination of the skin of the hands before and after treatment with the samples of the product was compared. Sampling from the skin of the hands of the testers was carried out using the wash method adopted for this purpose, using sterile gauze napkins dipped in a universal neutralizer (tween 80, histidine, cysteine, lecithin).

For hygienic processing of hands, the following method of application was used: apply at least 3 ml of the product to the hands and rub into the skin of the hands until it dries, but at least 30 s.

The data obtained during hygienic processing of the hands of the testers of the means are subjected to statistical processing and are presented in table No. 2.

Criteria for the effectiveness of the product: reduction of the total microbial contamination of the skin during hygienic processing of the hands by at least 95%; a decrease in the contamination of the skin contaminated by the test organism (E. coli strain 1257) by no less than 99.99%.

In experimental studies used a prototype of the tool according to example No. 1.

Thus, it was found that the death of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and poliomyelitis virus occurred in less than 30 s, while for the prototype sample the death of Pseudomonas aeruginosa and poliomyelitis virus occurred in 1 min, and the death of fungi Candida albicans - 2 minutes after contact with a sample of the product.

Table 3 presents the data obtained during the hygienic processing of the hands of the testers by the proposed tool.

It was found that hygienic treatment of the hands of the testers with the agent for 1 min leads to 100% death of the test culture applied to the hands. The level of total microbial contamination of the skin of the hands decreased by 98.26%. The number of gram-positive and gram-negative microorganisms also decreased by 97.50-100%, respectively.

A group of testers (10 people), consisting of men and women aged 30 to 70 years, took part in the study of the effectiveness of the disinfecting effect of the agent according to the invention. Hygienic treatment of the skin of the hands of the testers with the tool according to the above method and the frequency of use of the product from 1 to 4-5 times was not accompanied by a violation of the general well-being of the testers or by changes in the treated areas of the skin of the hands, which made it possible to evaluate the proposed tool as satisfactory, without causing side effects when hygienic processing of hands.

To establish the shelf life of the product, studies were conducted to study its stability.

For 2 months and 10 days under accelerated aging (at 50 ° C), three prototypes of the agent were observed. According to the "Instructions for conducting work to determine the shelf life of drugs based on the method of" accelerated aging "at elevated temperatures", M., 1974 - storage at 50 ° C reduces the observation time by 8 times, and thus the observation period in 2 months and 10 days is equivalent to 19 months at room temperature.

Tests of the stored samples were verified with the determination of all indicators controlled in accordance with the technical conditions, namely the appearance, color, odor, hydrogen ion activity index (pH), and the mass fraction of the active components included in the composition.

As a result of the observation, the preservation of all the existing disinfecting components without changes in the composition of the proposed means was established.

During the observation period, there were also no changes in the appearance, color and smell of the product.

Thus, the results obtained in this study indicate sufficient stability of the drug, which allows us to establish a period of 1.5 years for it.

Analyzing research data, we can draw the following conclusions.

Due to the joint interaction of three active disinfectants: ammonium compounds - alkyldimethylbenzylammonium chloride (HOUR) and N, N-bis (3-aminopropyl) dodecylamine (tertiary amine), as well as a polymer biocide - polyhexamethylene guanidine hydrochloride, the proposed agent has high biocidal action. The product has a wide spectrum of antimicrobial activity against gram-positive and gram-negative bacteria, yeast-like fungi of the Candida genus, viruses of causative agents of parenteral and enteric hepatitis, KOSAKI and ECHO, enterovirus infections, polio, rota and norovirus infections, HIV infections, influenza, etc. . type AH5N1, H1N1, adenovirus infection, herpes, cytomegaly. Thus, the proposed tool has fungicidal, bactericidal, tuberculocidal and virucidal activity.

The product is intended for hygienic processing of hands:

- medical personnel of medical organizations of any profile, ambulances, in emergency situations, in sanitary inspection rooms;

- laboratory workers (including bacteriological, virological, etc.); drugstores and drugstores;

- medical workers of preschool and school institutions, welfare institutions (nursing homes, people with disabilities, etc.), hospices, health resorts, military and penitentiary institutions;

- for hygienic processing of hands in sanitary inspection rooms of workers of perfumery, cosmetic, pharmaceutical and microbiological enterprises; food industry enterprises, public catering, industrial markets, trade (including cashiers and other persons working with banknotes);

- at public utilities, educational, cultural, recreational, sports, shopping centers, airports, railway stations and auto centers, public toilets;

- by the adult population (including children from the age of three) at home, on transport, in the subway, when visiting restaurants, cafes, etc.

Table 1 No. p / p Alkyldimethylbenzylammonium chloride with a chain length of C _l2 -C ₁₆ N, N-bis (3-aminopropyl) dodecyl amine PHMG hydrochloride Lipo-Senthol Hydro 40% lactic acid Perfume Water Technical result Content in wt.% The product has a high disinfecting effect, is convenient to use, can be easily removed if necessary, has a therapeutic effect in relation to damaged skin for a long time, the finished product retains its properties for 1.5-2 years one 0.1 Oj 0.25 0.3 0.1 0.1 rest 2 0.08 0.12 0.22 0.1 0.2 0.02 rest 3 0.12 0.08 0.28 0.2 0.3 0.08 rest four 0.128 * 0.1 0.25 0.2 0.2 0.1 rest Deterioration of technological properties 5 0.05 * 0.1 0.25 0.2 0.2 0.1 rest Reduced disinfecting effect 6 0.1 0.13 * 0.25 0.2 0.2 0.1 rest Deterioration of technological properties 7 0.1 0.05 * 0.25 0.2 0.2 0.1 rest Reduced disinfecting effect 8 0.1 0.1 0.3 * 0.2 0.2 0.1 rest Unjustified consumption of des. facilities 9 0.1 0.1 0.2 * 0.2 0.2 0.1 rest Reduced prolonged effect 10 0.1 0.1 0.25 0.35 * 0.2 0.1 rest Raising the pH of the product eleven 0.1 0.1 0.25 0.05 * 0.2 0.1 rest Reduced disinfecting effect 12 0.1 0.1 0.25 0.2 0.35 * 0.1 rest Raising the pH of the product 13 0.1 0.1 0.25 0.2 0.05 * 0.1 rest PH reduction fourteen 0.1 0.1 0.25 0.2 0.2 0.12 * rest Sharpen odor fifteen 0.1 0.1 0.25 0.2 0.2 0.01 * rest Odor reduction Note: * - the content of the component is beyond the stated limits.

table 2 Microorganisms Death time (min) The control 0.5 one 2 E. coli - - - + Staphylococcus aureus - - - + Pseudomonas aeruginosa - - - + Candida Albicans - - - + Polio virus (vaccine strain LSc 2 ab) - " " + Prototype example No. 1 E. coli - - - + Staphylococcus aureus - - - + Pseudomonas aeruginosa + - - + Candida Albicans + + - + Polio virus (vaccine strain LSc 2 ab) + - - + Table 3 Type of contamination of the skin of the hands Type of microflora The number of colony forming units (CFU) The effectiveness of disinfection at P = 0.95% before processing after processing Artificial E. coli 1560.00 ± 82.70 0 one hundred Natural Total microbial contamination 836.00 ± 180.22 13.00 ± 0.28 98.26 ± 0.35 Gram-positive microorganisms 143.75 ± 57.11 2.75 ± 0.83 97.50 ± 0.54 Gram-negative microorganisms 21.12 ± 6.89 0 one hundred

Claims (1)

An agent for disinfecting the skin, including alkyl dimethylbenzylammonium chloride, N, N-bis (3-aminopropyl) dodecylamine, liposentol hydro and water, characterized in that it additionally contains polyhexamethylene guanidine hydrochloride, 40% lactic acid and perfume, while alkyl dimethyl benz chloride is used with a chain length of C ₁₂ -C ₁₆ in the following ratio of components, wt.%:
alkyldimethylbenzylammonium chloride with chain length C ₁₂ -C ₁₆ 0.08-0.12 N, N-bis (3-aminopropyl) dodecylamine 0.08-0.12 polyhexamethylene guanidine hydrochloride 0.22-0.28 liposenthol hydro 0.1-0.3 40% lactic acid 0.1-0.3 perfume 0.02-0.1 water rest