RU2413496C2 - Alcohol-free scrub-up composition and method of using thereof - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to disinfectants and can be used in medicine for a scrub-up procedure. A group of inventions is characterised by an alcohol-free scrub-up composition and a method of scrubbing with using this composition. The scrub-up composition representing foam containing gas and liquid in the volume ratio 3:1 to 30:1 wherein a liquid portion contains didecyldimethylammonium chloride and/or polyhexamethylbuguanidine hydrochloride, a foaming agent, a gel-forming polymer, aluminium hydrochloride, pH regulator to 5.5±1.0 and water in a certain ratio in mass percent. The method of scrubbing wherein 2.5 g to 7.5 g of this composition is applied on the whole skin surface of both arms, including wrists and forearms, and rubbed for 3 to 5 minutes.

EFFECT: invention provides lower effective dose of a disinfectant, prolonged guaranteed time of residual antimicrobial action and reduced formation of gloves juice, faster scrub-up procedure.

8 cl, 4 tbl, 1 ex

Description

FIELD OF THE INVENTION

The invention relates to disinfectants and can be used in medicine for the treatment of surgeons hands.

State of the art

Microorganisms that live on the skin of the hands are divided into transient microflora and resident microflora. Transient flora is represented by various microorganisms that are epidemiologically dangerous: E. coli, Klebsiella, Pseudomonas, Salmonella, St. aureus and others, and can be easily removed during normal hand washing or with antiseptic treatment. Resident microorganisms colonize the surface and deeper layers of the skin, including the ducts of the sweat glands, and are normal inhabitants of healthy skin. If the skin is damaged or irritated as a result of inadequate hand treatment methods, transient microflora can permanently infect the skin, forming a new resident flora of the hands, which is more dangerous in the epidemic sense. In a hospital, it is possible to colonize the skin of the hands with hospital strains of microorganisms. Hospital strains of microorganisms are formed from pathogenic and conditionally pathogenic microbes that become infectious under certain conditions (most often in hospital settings). In this case, the hands of medical workers can be a factor in the transmission of infection, and in some cases even become a reservoir of infection.

In accordance with the standards of the Ministry of Health of the Russian Federation, the criterion for the effectiveness of skin antiseptics intended for the treatment of surgeons hands is to reduce the total microbial contamination of the skin of the hands by 100% to prevent infection of the patient’s tissues from the hands of the surgeon with damaged gloves. Skin antiseptics used to treat surgeons' hands should have a prolonged (residual) antimicrobial effect that prevents the growth of resident microorganisms migrating from the deeper layers of the skin for at least 3 hours.

The traditional method of treating surgeons' hands is to apply 5 ml of a skin antiseptic (10 ml total) to a previously washed dry hand with a liquid dispenser and rub it into the skin for a total of 5 minutes, paying particular attention to the interdigital the gaps, as well as the skin around the nails, on the wrists and forearms. During the whole time of rubbing, the skin should be kept moist. Then let the skin dry and put on sterile rubber gloves.

The main disadvantage of this method is that the antiseptic is applied to the hands, and not to the entire surface of the hands, and then distributed manually on the skin of the hands. This creates the risk of an uneven distribution of antiseptics, which can lead to insufficient disinfection of certain areas of the skin, which causes an increase in the consumption of antiseptics. The consequence of the overspending of the antiseptic is an increase in the time it dries on the skin and, therefore, an irrational increase in the total time spent on surgical disinfection of the hands.

From European patent application EP 1666073 A1, pyroglutamic acid-based skin antiseptics are known which contain a volatile solvent (preferably ethyl alcohol), which are applied to the hands in the form of air foam, followed by rubbing this foam before drying. As a foaming agent, they contain an anionic surfactant. Since pyroglutamic acid is effective only in an acidic environment, these antiseptics should have the lowest possible pH value. It is stated that they have bactericidal and virucidal activity and a prolonged antimicrobial effect, however, the patent description does not contain data on these properties and a detailed description of the method of application, which does not allow us to evaluate the possibility of using these antiseptics for treating surgeons hands.

The first drawback of antiseptics of this composition is that alcohol drowns the skin. With daily and repeated use during the working day, this leads to dry skin and a violation of its barrier functions, up to the development of dermatitis and allergic reactions. The second disadvantage of these antiseptics is that they have a low pH and can cause severe skin irritation up to a chemical burn. The third disadvantage of these antiseptics is that the foam obtained from them is unstable and has a low multiplicity (the ratio of the total volume of the foam to the volume of the liquid of which it consists), since alcohol inhibits foaming.

Alcohol-free antiseptics are rarely used to treat the hands of surgeons, although they are less expensive than alcohol-containing products and are better tolerated by the skin. This is due to the fact that replacing alcohol with water significantly reduces the antimicrobial activity of the active substances, slows the drying of the antiseptic on the skin and reduces the prolonged effect. The decrease in antimicrobial activity forces to increase the content of active substances many times, which further slows down the drying. The Russian Ministry of Health authorized the use of only five alcohol-free skin antiseptics for the treatment of surgeons' hands: Veltosphere, Aquin, Teflex A, Triosept-Aqua and Amidin Aqua, presented in Table 1 below.

Table 1 Alcohol-free antiseptics approved for the treatment of surgeons Tradename Active substances Mode of application Prolonged action Veltosphere Quaternary ammonium clathrate with urea (0.2%) 5 ml (5 g) of the product are applied twice to previously washed dry hands and rubbed into the skin, keeping it moist for 5 minutes. Sterile gloves are worn after the product has completely dried (drying time is not regulated). At least 3 hours Aquinas Polyhexamethylene biguanidine phosphate (1.0%) At least 3 hours Teflex A Polyhexamethylene biguanidine hydrochloride (0.4%) - Triosept Aqua Alkyldimethylbenzylammonium chloride (0.37%) At least 3 hours Didecyldimethylammonium chloride (0.03%) Polyhexamethylene biguanidine phosphate (0.8%) Amidin Aqua Alkyldimethylbenzylammonium chloride (0.25%), 5 ml (5 g) of the product are applied to previously washed dry hands and rubbed for 2.5 minutes. Then another 5 ml (5 g) of the product is applied and rubbed for another 2.5 minutes. Residues are removed by wiping hands with sterile gauze wipes or rinsing them with sterile water, followed by drying hands with sterile wipes. 4 hours N, N-bis (3-aminopropyl) dodecylamine (0.51%)

From Table 1 it follows that all of these agents have an effective dose of 10 ml (10 g), the total processing time exceeds 5 minutes (in fact, it is 7-10 minutes), and the guaranteed time of residual antimicrobial action is not more than 4 hours.

None of the known antiseptics used to treat the hands of surgeons suppresses the formation of the so-called “glove juice” due to sweating in the confined space of the gloves. Meanwhile, maintaining dry hands is important, as it creates a feeling of comfort for surgeons and reduces the likelihood of infection of the patient’s tissue with damaged gloves.

Disclosure of invention

The first objective of the invention is the creation of an alcohol-free skin antiseptic composition for treating the hands of surgeons, which is a foam with a multiplicity of 3 to 30, that is, occupying a 3-30 times larger volume than the liquid contained in it. Such a foam is much easier to evenly distribute on the skin of the hands without overspending the antiseptic composition. With subsequent rubbing, the foam collapses, leaving a thin layer of liquid that dries quickly on the skin with the formation of an invisible film that provides a residual antimicrobial effect. When the multiplicity is less than 3, the above advantages of the foam form are significantly reduced, and when the multiplicity is more than 30, the volume of the foam becomes too large, which greatly complicates the use of the proposed composition. The optimal ratio of foam is in the range from 10 to 20.

Thus, the first object of the invention is an alcohol-free skin antiseptic composition for treating the hands of surgeons, consisting of a foam containing gas and liquid in a volume ratio of from 3: 1 to 30: 1 (preferably from 10: 1 to 20: 1), characterized in that it includes the following components in mass percent:

at least one antimicrobial agent from 0.01 to 1.00, at least one foaming agent from 0.01 to 0.50, at least one gelling polymer from 0.05 to 5.00, at least one aluminum salt from 0.01 to 25.00, at least one pH regulator from 0.01 to 0.50 and water rest.

The composition has a pH close to the physiological pH of the skin, 5.5 ± 1.0. Preferably, the composition has a pH of approximately 5.5.

In a particular embodiment, as at least one antimicrobial agent, the composition includes at least one substance selected from the group consisting of a quaternary ammonium salt, a polyguanidine salt and an aliphatic amine.

In a preferred embodiment, as a quaternary ammonium salt, the composition includes didecyldimethyl ammonium halide, and as didecyldimethyl ammonium halide, it includes didecyldimethyl ammonium chloride (DDAC).

In a preferred embodiment, it includes polyhexamethylene biguanidine hydrochloride (PHMHC) as the polyguanidine salt.

In a preferred embodiment, the composition includes DDAH and PHMHC in a weight ratio of 1: 5 to 5: 1.

In a preferred embodiment, the composition includes N, N-bis (3-aminopropyl) dodecylamine as an aliphatic amine.

In a particular embodiment, as at least one blowing agent, the composition includes at least one surfactant selected from the group consisting of anionic surfactant, nonionic surfactant and amphoteric surfactant.

In a preferred embodiment, as at least one blowing agent, the composition includes at least one surfactant selected from the group consisting of alkyl polyglucoside, alkyl dimethyl amine oxide and alkyl amidopropyl dimethyl amine oxide.

In a preferred embodiment, as at least one blowing agent, it includes at least one surfactant selected from the group consisting of C ₈ -C ₁₀ alkylpolyglucoside, cocoalkylpolyglucoside, lauryl dimethyl amine oxide, myristyldimethyl amine oxide and cocamidopropyl dimethyl amine oxide.

In a particular embodiment, as at least one gelling polymer, the composition includes at least one material selected from the group consisting of xanthan gum, guar gum, locust bean gum, dextrin, mucopolysaccharide and cellulose derivative.

In a particular embodiment, as the at least one aluminum salt, the composition includes at least one material selected from the group consisting of aluminum hydrochloride, aluminum sulfate and potassium alum.

In a preferred embodiment, the composition includes at least one aluminum salt of aluminum hydrochloride.

In a particular embodiment, as at least one pH regulator necessary to achieve a pH close to a physiologically favorable skin pH (5.5 ± 1.0), the composition may include any alkaline and / or acidic substances, compatible with its other components and well known to those of ordinary skill in the art. Without seeking to be limited to any particular list of such substances, the composition may include at least one substance selected from the group consisting of lactic acid, citric acid, acetic acid, salts of these acids with alkali metals, sodium hydroxide and potassium hydroxide.

DDAH and PHMHH are antimicrobial substances that are highly active against gram-positive bacteria, but are not active enough against gram-negative bacteria, tuberculosis mycobacteria and fungi and are ineffective against simple viruses (enteroviruses, poliomyelitis virus, etc.). It was unexpectedly discovered that when DDAH and PHMHC are included in the composition in a mass ratio of 1: 5 to 5: 1, a synergistic increase in their activity occurs, in particular fungicidal and virucidal activity.

Tables 2-4 show the data on in vitro antimicrobial activity obtained by the method of batistov test objects in accordance with the “Methods of testing disinfectants to assess their safety and effectiveness” (Moscow, 1998, part 2). S. aureus (strain 906), E. coli (strain 1257), P. aeruginosa (strain ATCC 27853), Mycobacterium B ₅ test model of the tuberculosis pathogen, C. albicans (strain 15), and virus were used as test cultures poliomyelitis type 1 (vacc. strain LSc 2ab) with an exposure of 5 minutes The criterion for the effectiveness of disinfection of cambric test objects is -100% with the convergence of the results of three replicates.

table 2 Antimicrobial activity of DDAC, PHMHH and mixtures thereof Antimicrobial substance Concentration% Bacteria (except Mycobacterium tuberculosis) Mycobacterium tuberculosis Mushrooms Viruses DDAH 0.05 0.25 1.00 2.00 PHMHH 0.10 2.00 2.00 2.00 DDAH + PHMHH 5: 1 0.015 0.10 0.50 0.10 DDAH + PHMHH 1: 2 0.010 0,075 0.25 0,050 DDAH + PHMHH 1: 5 0,025 0.15 0.25 0,075

To facilitate foaming and stabilize the foam, a foaming agent is included in the composition of the composition. It has been found that the most preferred blowing agents are alkyl polyglucosides, alkyl dimethyl amine oxides and alkyl amidopropyl dimethyl amine oxides containing C ₆ -C ₁₈ alkyls. Non-limiting examples of such blowing agents include, but are not limited to, C ₈ -C ₁₀ alkyl polyglucoside, cocoalkyl polyglucoside, lauryl dimethyl amine oxide, myristyldimethyl inocide and cocamidopropyl dimethyl amine oxide. It was found that all and each of the listed blowing agents synergistically enhance the antimicrobial activity of the proposed composition (table 3).

Table 3 The effect of a foaming surfactant on the antimicrobial activity of a mixture of DDAC and PHMHC Antimicrobial substance The concentration of the sum DDAH + PHMHH,% Bacteria (except Mycobacterium tuberculosis) Mycobacterium tuberculosis Mushrooms DDAH + PHMHH 1: 2 0.010 0,075 0.25 The same + C ₈ -C ₁₀ -alkylpolyglucoside (1: 2: 2) 0.005 0,050 0.15

Aluminum salt is included in the composition in order to block the ducts of the sweat glands, which are the habitat of resident microorganisms. Not trying to limit themselves to any particular theory, they suggest that this, firstly, prevents the migration of resident microorganisms to the surface of the skin of the hands and, thus, promotes a prolonged antimicrobial effect, and secondly, inhibits the formation of “glove juice”. The most preferred aluminum salt is Al ₂ Cl _n (OH) _6-n (the so-called aluminum hydrochloride), known as the active component of antiperspirants. In addition to the above expected properties, the inclusion of an aluminum salt in the composition of the composition unexpectedly increases its bactericidal and fungicidal activity (Table 4).

Table 4 The effect of aluminum hydrochloride on the antimicrobial activity of a mixture of DDAC and PHMHC Antimicrobial substance The concentration of the sum DDAH + PHMHH,% Bacteria (except Mycobacterium tuberculosis) Mycobacterium tuberculosis Mushrooms DDAH + PHMHH 1: 2 0.010 0,075 0.25 The same + aluminum hydrochloride (1: 2: 5) 0.005 0,025 0.10

For thickening, the composition includes a gelling polymer. It was found that it forms an invisible film on the skin, providing a residual antimicrobial effect, and in this regard serves as a useful complement to PHMHC, which also has film-forming properties. In addition, it turned out that the above gel-forming polymers are able to perform two more functions, namely to further stabilize the foam and absorb sweat on the skin of the hands, while remaining dry. Thanks to the addition of a gel-forming polymer, the hands treated with the proposed antiseptic composition retain a dry feeling in the gloves for a long time even with such a content of aluminum hydrochloride that is insufficient to completely block the ducts of the sweat glands.

The second objective of the invention is to provide a method for processing the hands of surgeons using the proposed antiseptic composition, which provides uniform disinfection of the entire surface of the skin, reducing the consumption of antiseptic compositions and reducing processing time.

Thus, the second object of the invention is a method for processing the hands of surgeons using the proposed alcohol-free skin antiseptic composition, characterized in that from 2.5 g to 7.5 g of this composition is applied to the entire surface of the skin of both hands, including wrists and forearms, and rubbed over a period of 3 to 5 minutes.

The implementation of the invention

The following example is given only to illustrate an inventive idea. Nothing in this section of the description should be construed as limiting the scope of the claims. It should be clear that the average person familiar with the ideas of the present invention, can use its main distinguishing features and make equivalent replacements to achieve the task and without deviating from the spirit and scope of the present invention.

Example 1

The liquid portion of the composition of the invention is prepared by methods well known to those of ordinary skill in the art. An illustrative example of the liquid part of the composition has the following composition:

didecyldimethylammonium chloride 0.2 g polyhexamethylene biguanidine hydrochloride 0.4 g C ₈ -C ₁₀ -alkylpolyglucoside 0.3 g xanthan gum 0.5 g aluminum hydrochloride 0.5 g sodium citrate 0.2 g (up to pH 5.5), water up to 100 g

The resulting liquid is transferred into an unpropellent package equipped with a dispenser with a foam-generating nozzle from Airspray NV (Netherlands). On the entire surface of both hands, including the wrists and forearms, 2.2 g of the composition, including this liquid in the form of a 15-fold air foam, are twice applied and then rubbed until completely dry (a total of 4 minutes).

Performance indicators are determined in accordance with the “Methods of testing disinfectants to assess their safety and effectiveness” (Moscow, 1998).

The effectiveness of disinfection in the treatment of surgeons' hands (reducing the total microbial contamination of the skin of the hands after washing twice with water and soap for 2 minutes and twice processing 2.2 g of the composition (3 pump strokes) for 4 minutes) met the required criteria and amounted to 100% .

A prolonged (residual) antimicrobial effect was established in the treatment of surgeons' hands after 5 hours, which was estimated by the number of sterile samples (lack of growth of microorganisms) in more than 50% of the number of samples taken from testers who handled the drug.

This composition is active against gram-positive and gram-negative bacteria (including pathogens of nosocomial infections and tuberculosis), has fungicidal (against fungi of the genus Candida) and virucidal (tested on type 1 polio virus). In an in vitro test, the time of complete death of bacteria (except tubercle bacillus) was 30 seconds, and mycobacterium tuberculosis died after 1 min.

Thus, the decrease in the total microbial contamination of the skin of the hands is 100%, the duration of the residual antimicrobial effect is at least 5 hours. The product does not cause skin irritation and allergic reactions, does not leave a sticky feeling on the hands. All testers noted a significant decrease in glove juice formation compared to the known skin antiseptics shown in Table 1.

These results allow us to state the following advantages of the proposed composition:

(1) the time for processing hands was reduced by 1.75-2.5 times (from 7-10 minutes to 4 minutes);

(2) the effective dose is reduced by 2 times (from 10 g to 4.4 g);

(3) the guaranteed time of residual antimicrobial action has been increased (from 3-4 hours to 5 hours);

(4) the formation of “glove juice” is significantly reduced.

Information sources

1. Application for a European patent EP 1666073 A1.

2. Instruction No. 24-30 / 07I on the use of the disinfectant - skin antiseptic "Veltosphere" (NPO "VELT", Russia), Moscow, 2007.

3. Instructions for use of the disinfectant "Aquin" IE "Inkraslav" (Republic of Belarus), Moscow, 2003.

4. Instructions for use of the disinfectant (skin antiseptic) Teflex A (ZAO Soft Protector, Russia), St. Petersburg, 2007.

5. Instructions for use of the disinfectant (skin antiseptic) Triosept-Aqua (NPO Spetsintez LLC, Russia), St. Petersburg, 2007.

6. Instruction No. 21 on the use of Amidin Aqua disinfectant (ZAO Petrospirt, Russia), St. Petersburg, 2007.

Claims (8)

1. Alcohol-free skin antiseptic composition for treating the hands of surgeons, which is a foam containing gas and liquid in a volume ratio of 3: 1 to 30: 1, in which the liquid part includes the following components, wt.%:
didecyldimethylammonium chloride and / or polyhexamethylene biguanidine hydrochloride from 0.01 to 1.00 foaming agent from 0.01 to 0.50 gelling polymer from 0.05 to 0.50 aluminum hydrochloride from 0.01 to 2.00 pH regulator 5.5 ± 1.0 from 0.01 to 0.50 water rest 2. The composition according to claim 1, in which its liquid part includes didecyldimethylammonium chloride and polyhexamethylene biguanidine hydrochloride in a mass ratio of from 1: 5 to 5: 1. 3. The composition according to claim 1, in which its liquid part includes, as a foaming agent, a substance selected from the group consisting of alkyl polyglucoside, alkyl dimethyl amine oxide and alkyl amidopropyl dimethyl amine oxide. 4. The composition according to claim 3, in which its liquid part includes, as a foaming agent, a substance selected from the group consisting of C ₈ -C ₁₀ -alkyl polyglucoside, cocoalkyl polyglucoside, lauryl dimethyl amine oxide, myristyldimethyl amine oxide and cocamidopropyl dimethyl amine oxide. 5. The composition according to claim 1, in which its liquid part includes, as a gelling polymer, a substance selected from the group consisting of xanthan gum, guar gum, locust bean gum, dextrin, mucopolysaccharide and cellulose derivative. 6. The composition according to claim 1, in which its liquid part includes, as a pH regulator, a substance selected from the group consisting of lactic acid, citric acid, acetic acid, salts of these acids with alkali metals, sodium hydroxide and potassium hydroxide. 7. The composition according to claim 1, in which the volume ratio of said gas to the liquid part is from 10: 1 to 20: 1. 8. A method for processing the hands of surgeons using an alcohol-free skin antiseptic composition according to any one of claims 1 to 7, characterized in that from 2.5 to 7.5 g of this composition is applied to the entire surface of the skin of both hands, including wrists and forearms, and rubbed over a period of 3 to 5 minutes.