SK500352013U1 - Disinfection product, disinfection method and use of disinfectant - Google Patents

Description

Technical field

The invention relates to a disinfectant having a broad spectrum of action against both microbes and viruses, particularly suitable for small areas and medical devices, the use of such a preparation and a method of disinfection.

BACKGROUND OF THE INVENTION

The most commonly used disinfection in hospitals and health care is alcohol based products for small areas by spraying. It is a disinfection of medical devices, trolleys, handles, handles, devices, etc. At these sites, the highest transmission of nosocomial infections occurs, and therefore the emphasis is on high microbial efficacy by disinfection tested under stress conditions.

Alcohols are the most commonly used disinfectant media for several reasons. They are inexpensive compared to other active substances, are not corrosive, do not leave residual residues on disinfected surfaces and have a broad bactericidal spectrum of microbial effect. However, it is known that they already have a worse effect on certain fungi and enveloped viruses, non-enveloped viruses are ineffective and mycobacteria multiply in the presence of alcohol. The disadvantage of alcohols is that they damage polymers and plastics and are highly flammable.

Quaternary ammonium compounds (KAS), e.g. benzalkonium chloride or alkyl dimethyl ammonium chloride do not in themselves have a significant effect on the inactivation of microorganisms, but in combination with alcohols they are effective against bacteria, pathogenic fungi and enveloped viruses. A worse effect is recorded on mycobacteria. The combination of alcohol and CAS is used most commonly in commercial products, but is insufficient for use in areas at high risk of infection.

One of the options for increasing the effectiveness of the existing alcohol disinfection on small areas by spraying, by achieving full virucidal effect is the addition of aldehydes (today the most common combination of glutaraldehyde, glyoxal). Their use in the future will be limited to glutaraldehyde only, as glyoxal will be excluded from the list of authorized biocidal substances under the BPD (Biocidal Product Directive). In general, there is a trend of slow withdrawal from the use of aldehydes, as they may be carcinogenic or potentially carcinogenic, bacteria resistant to glutaraldehyde, and recent reports indicate that they cause severe asthma and other health problems.

- 2 A scientific article from the Brazilian Journal of Pharmaceutical Sciences, vol.45, N.2, abr./Jun., 2009, lists the minimum inhibitory concentrations (MICs) of disinfectants and / or sterilizers, but does not mention glycolic acid or drawbar. disinfectant effect.

US 4,346,043 describes the microbial activity of glycolic acid ester (ester-amide) derivatives, but does not mention glycolic acid itself.

US 2010/0151046 and US 7,144,846 disclose glycolic acid as one of many variants for adjusting the pH of a solution. However, according to the authors, it is not the first choice for pH adjustment.

US 6,368,610 discloses an antimicrobial product for cleaning and disinfecting production equipment in food, brewing or dairies containing an inorganic acid (or mixture), an organic acid containing 30 to 70%, e.g. glycolic acid or from 70 to 30% acetic acid, which is active on Gram + and Gram-bacteria and yeast. It does not mention the use in medical and hospital facilities for the disinfection of surfaces and surfaces, nor does it mention the effects on viruses, mycobacteria and the TB strain.

The essence of the technical solution

The present technical solution is the disinfectant, especially suitable for small areas, surfaces, and a device which is characterized in that it comprises glycolic acid, at least one C _r C6 alcohol, and at least one quaternary ammonium compound selected from the group consisting of C ₈ - C _1-6 -alkylbenzyldimethylammonium chloride, C ₈ -C ₁₆ -alkyldimethylammonium chloride and di (C ₈ -C ₁₆ -alkyl) dimethyl ammonium chloride.

The present invention also relates to a method for the disinfection of surfaces and medical devices, which comprises applying a mixture of glycolic acid, at least one C 1 -C 6 alcohol, and at least one quaternary ammonium compound selected from the group consisting of C to the disinfected area or medical device. ₈ -C _1-6 -alkylbenzyldimethylammonium chloride, C ₈ -C 16 -alkyl dimethylammonium chloride and di (C ₈ -C ₁₆ -alkyl) dimethylammonium chloride.

The object of the present the invention is also the use of a mixture of glycolic acid, at least one C _{r C6} alcohol, and at least one quaternary ammonium compound selected from the group consisting of _C8--Ci6 alkylbenzyIdimetylamóniumchlorid, _C-8 -Ci6 alkyIdimetylamóniumchlorid and di (C ₈ alkyl CI6 dimethylammonium chloride, for disinfection, in particular for the disinfection of surfaces and medical devices.

The advantage of the technical solution is to increase the microbial and virucidal efficacy of commercial products on the market and thus extend the applicability of disinfection to areas with a high risk of infection, without the use of problematic aldehydes. Surprisingly, it has been found that glycolic acid contributes to the full virucidal effect.

Preferably, the disinfectant comprises 50 to 88 wt. %, preferably 55 to 80 wt. %, _Cl-C6 alcohol or a mixture of _Ci-C6 alcohols. Preferably C _{r C6} alcohol is selected from the group consisting of ethanol, 1-propanol, 2-propanol.

Further, the composition preferably comprises 0.1 to 5 wt. %, preferably 0.5 to 2 wt. %, quaternary ammonium compounds or mixtures of quaternary ammonium compounds. Preferably, the quaternary ammonium compound is selected from the group of agents such as Bardac 22 and various concentrated variants thereof, Bardac LF, Barquat CB, Barquat DM, Barquat MB and Barquat BB (all from Lonza) or Protectol KLC50 (BASF).

To enhance the microbial and virucidal activity, the composition preferably contains 7 to 12 wt. %, preferably 7 to 10 wt. %, glycolic acid.

The residue up to 100 wt. % of the disinfectant is then water.

The formulation according to the invention comprises as one of the main antimicrobial components C _t -C ₆ alcohol. The addition of the quaternary ammonium compound then potentiates the microbial effect of the alcohols and increases the effect against pathogenic fungi and enveloped viruses (e.g., HIV, HB V, etc.). In addition, it has good cleaning and wetting properties. The glycolic acid content required is effective to ensure full virucidal activity.

As additional ingredients, adjuvants such as perfumes can be used in the disinfectant, in the case of the formation of a gel structure it is possible to incorporate gelling agents and associated suitable neutralizing agents for high alcohol content, colorants and solubilizers of perfume compositions, or other auxiliaries suitable disinfectants.

EXAMPLES

Examples 1-7: Preparation and composition of disinfectants

All raw materials are in liquid form, cold water soluble. The raw materials were mixed at room temperature to give a homogeneous, slightly yellowish solution that smelled of alcohols.

Example

raw material 1 2 3 4 5 6 7 Ethanol [g] 45 45 80 45 1-Propanol [g] - - - - 45 45 55 2-Propanol [g] 35 35 - 25 30 30 - Didecyldimethylammonium chloride [g] - - 1 - 1 1 1 C12-C16 dimethylbenzylammonium chloride [g] 0.5 - - 0.5 1 - - Cn-Cig dimethylbenzylammonium chloride [g] - 0.5 - - - - - Glycolic acid [g] 10 10 10 10 7 10 10 Water to 100g

Example 8: Microbiological testing

The tests were carried out under the auspices of the State Institute of Public Health in Prague and the accredited laboratory Chemila. The formulations were tested by both the suspension method and the method of disinfection of contaminated carriers that correspond to the actual conditions of use. The results are summarized in Table 1 below: Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values, Table 2: Results for the formulation of Example 6, and Table 3: Results for the formulation of Example 7th

Methods of testing the efficacy of disinfectants by suspension methods and on solid surfaces (method carrier), used microbes:

A. Evaluation of bactericidal, fungicidal (microscopic yeast fungi) and sporicidal efficacy of the product:

a. Suspension micromethods determine the minimum inhibitory concentration (MIC), the minimum bactericidal concentration at a protein load at 10 min exposure (MBC-B), and the minimum bactericidal concentration at aqueous exposure at various exposures (MBC).

b. The standard suspension method evaluates fungicidal (MFC - microscopic yeast fungi) and sporicidal (MSC) activity of substances in aqueous solution even at protein load

- 5 at different exposures and bactericidal efficacy (MBC) at different working solution temperature and protein loading. (CSN EN 1650 (66 5203): Chemical disinfectants and antisepticsQuantitative test using a suspension to determine the fungicidal or anti-yeast effect of chemical disinfectants and antiseptics used in food, industry, households and public establishments - Test method and requirements (Phase 2 / degree D).

c. The artificially contaminated carrier method mimics the practical use of the preparations in disinfection by immersion, wiping and spraying. 25 x 25 mm glass or metal carriers are contaminated with a broth suspension by St. aureus, E. coli. and C.alcicans. After drying, they are disinfected by immersion in the test solution or by wiping or spraying with the solution. Surviving microbes are demonstrated by imprinting the carriers on an agar plate and subsequent culturing. The number of microbial colonies grown on the fingerprint relative to the control fingerprints of the non-disinfected carriers is evaluated.

Strains from the State Type Culture Collection (CNCTC) at SZÚ Praha are used for testing:

Staphylococcus aureus Mau 43/60 SG511 Escherichia coli Ec 324/70 NCTC 8196 Pseudomonas aeruginosa Ps 79/70 NCTC 6749, ATCC 19582 Proteus vulgarit PrO 10/52 Serratia marcescens Sm 29/80 JF 246 Enterococcus faecium Page 6/58 FDAM19, ATCC 10541 Candida albicans 49/64 SC 1539 Bacillus subtilis (spores) Bs 4/42

bioindicators for hot air sterilization

Bacillus subtilis (10 ⁶ CFU / ml) ATTC 9372

The density of the bacterial suspensions was 10 ^{8 "9} CFU / ml. (CFU - Coloniform Units).

Test samples are considered 100% and diluted with sterile distilled water to the required concentrations prior to use. To monitor the effect of protein substances on efficacy, samples are diluted with 20% bovine serum or plate broth. A decrease in CFU / 1 ml by 5 to 6 orders is considered satisfactory. Neutralizer is added to the culture medium: Tween 80 (3%), Cysteine (0.1%), Lecithin (0.3%), Sodium Sulfate (0.5%).

B. Evaluation of the virucidal efficacy of the product:

- 6 a. The suspension method of the direct effect of the disinfectant on the model virus suspension determines the MVC (minimum virucidal concentration of the substance) required to inactivate the virus in an aqueous or protein environment.

b. The contaminated carrier method mimics the use of the preparation in practice. Carriers of various materials (glass, metal, etc.) are contaminated with the virus suspension and, after disinfection by rubbing, dipping or spraying, the effectiveness of the preparation is evaluated by plaque method.

The strains from the State Type Culture Collection (CNCTC) at SZÚ Praha are used for testing:

E. coli bacteriophage ph174 (NCTC 13706-B1 shown on host E. coli (NCTC 13706/427/84

The titre of the viral suspension used is 10 ⁷ - ⁸ PFU / ml. (PFU).

Test samples are considered 100% and diluted with sterile distilled water to the required concentrations prior to use. In monitoring the effect of protein substances on efficacy, samples are diluted with 20% bovine serum. A decrease in CFU / 1 ml by 4-5 orders is considered satisfactory.

C. Evaluation of fungicidal efficacy of the preparation on microscopic filamentous fungi

The suspension modified method, in which 0.1 ml of the fungal spore suspension is mixed with 10 ml of the test solutions, and after time exposures, is inoculated with 0.1 ml into liquid and solid soil. Growth of fungi to sporulation in the blank on the surface of liquid soil and growth of colonies on solid soil were evaluated.

Strains from the mythological collection of cultures of Charles University in Prague are used for testing:

Aspergillus niger

Penicillium aurantiogriseum

The number of spores in the suspension is about 10 ⁶ CFU / ml. (CFU). A decrease in CFU / 1 ml by 5 to 6 orders is considered satisfactory.

The percentages given correspond to the dilution of the formulation according to Example 6 and 6, respectively. 7, water.

Tab. 1: - MIC and MBC values

Composition according to example 6: Composition according to Example 7: MIC 0,12% 0,12% MBC 3,3% 3,3%

Tab. 2: Results for the formulation of Example 6

germ Suspension test Disinfection of contaminated carriers Min. concentration / Exposure Min. concentration / Exposure Staphylococcus aureus 3.3% / 10 min. * 100% - 50% / 5 min. Escherichia coli 3.3% / 10 min. * 100% - 50% / 5 min. Pseudomonas aeruginosa 3.3% / 10 min. * tested Proteus vulgaris 3.3% / 10 min. * tested Seratia marcescens 3.3% / 10 min. * tested Candida albicans 100% -50% / 4 min. * 100% -50% / 5min. Aspergillus niger 100% - 50% / 5 min. * 100% - 50% / 5 min. Penicillium aurantiogriesum 100% - 50% / 5 min. * 100% - 50% / 5 min. Mycobacterium terrae 100% / 5 min. * tested Mycobacterium avium 100% / 5 min. * tested E. coli bacteriophage Φ174 100% / 4 min. * 100% / 5 min.

* Protein tested

Tab. 3: Results for the formulation of Example 7

germ Suspension test Disinfection of contaminated carriers Min. concentration / Exposure Min. concentration / Exposure Staphylococcus aureus 3.3% / 10 min. * 100% - 50% / 5 min. Escherichia coli 3.3% / 10 min. * 100% - 50% / 5 min. Pseudomonas aeruginosa 3.3% / 10 min. * tested Proteus vulgaris 3.3% / 10 min. * tested Seratia marcescens 3.3% / 10 min. * tested Candida albicans 100% -50% / 4 min. * 100% -50% / 5min. Aspergillus niger 100% - 50% / 5 min. * 100% -50% / 5min. Penicillium aurantiogriesum 100% - 50% / 5 min. * 100% - 50% / 5 min. E. coli bacteriophage Φ174 100% / 4 min. * 100% / 5 min.

* Protein tested

Examples 9-11: Comparative Examples of Microbiological Testing

The efficacy of three samples of disinfectants was compared: Example 9: alcohol

Example 8: Alcohol + CAS

Example 11: alcohol + KAS + glycolic acid

Samples were prepared by mixing the ingredients at room temperature.

The results are obtained by the method of disinfection of contaminated carriers, in 100% concentration of the preparation, with an exposure time of 5min.

raw material Example 9 10 11 1-Propanol [g] 45 45 45 2-Propanol [g] 25 25 30 Didecyldimethylammonium chloride [g] - 1 1 Glycolic acid [g] - - 10 Water to 100g to 100g to 100g

Example

tribe 9 10 11 Staphylococcus aureus + + + Escherichia coli + + + Candida albicans + + + Aspergillus niger + / 15min + + Penicillium aurantiogriesum + / 15min + + E. coli bacteriophage Φ174 - - +

Industrial usability

The present composition can be used in liquid form on small areas by spraying with efficacy even on small non-enveloped viruses. It is mainly used in high-risk areas such as ICU, ARO, ambulance, ambulance, all surgical fields (neurosurgery, urology, gynecology, etc.), burn center, neonatology and others. The product is applicable, inter alia, to all hospital and health departments, retirement homes, laboratories, veterinary and food industries and others.

Claims (6)

PROTECTION REQUIREMENTS Disinfectant, characterized in that it comprises glycolic acid, at least one C 1 -C ₆ alcohol, at least one quaternary ammonium compound selected from the group consisting of C ₁ -C ₁₆ -alkyl benzyidimethylammonium chloride, C ₁ -C ₁₆ -alkyldimethylammonium _chloride and di (C ₆ -C ₁₆ -alkyl) dimethylammonium chloride. Disinfectant composition according to claim 1, characterized in that it contains 50 to 88 wt. % C _r C ₆ alcohol and a mixture of _C-C6 alcohol, 0.1 to 5 wt. % of a quaternary ammonium compound or a mixture of quaternary ammonium compounds, 7 to 12 wt. % glycolic acid and water. The disinfectant composition of any one of claims 1 and 2, further comprising ingredients selected from the group consisting of excipients, gelling agents, neutralizing agents, coloring agents, and solubilizers of perfume compositions. Method of disinfecting surfaces and medical devices, characterized in that a disinfectant according to any one of claims 1 to 3 is applied to the disinfected area or medical device. 5. The use of a mixture of glycolic acid, at least one C _r C ₆ alcohol and at least one quaternary ammonium compound selected from C ₁₆ -C -alkylbenzyldimetylamóniumchlorid _g, C _g, C ₆ -alkyldimetylamóniumchlorid and di _{(Cg-C 16} -alkyl) dimethylammonium chloride , for disinfection. Use according to claim 5, characterized in that the mixture contains 50 to 88 wt. % Of a C 1 -C ₆ alcohol or a mixture of C 1 -C ₆ alcohols, 0.1 to 5 wt. % of a quaternary ammonium compound or a mixture of quaternary ammonium compounds, 7 to 12 wt. % glycolic acid.