CZ2012281A3 - Disinfectant, process of its use and disinfection method - Google Patents

Abstract

The present invention describes the use of a mixture of glycolic acid, at least one carbonyl alcohol, and at least one quaternary ammonium compound selected from the group consisting of C.sub.8. .Alpha.-alkyl benzyl dimethyl ammonium chloride, C.sub.8.-C.sub.16-alkyl dimethyl ammonium chloride and di (C.sub.8. 16.n.-alkyl) dimethyl ammonium chloride, for disinfection. It also describes a suitable disinfectant and disinfection of surfaces and medical devices by applying a disinfectant.

Description

Technical field

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

BACKGROUND OF THE INVENTION

The most commonly used disinfectant in hospitals and healthcare is spray-based alcohol based products. It is a disinfection of medical devices, carts, handles, handles, devices, etc. At these places the highest transmission of nosocomial infections occurs and therefore the high microbial effectiveness of disinfectants tested under stress conditions is emphasized.

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 are already less effective 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), such as 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 seen on mycobacteria. The combination of alcohol and CAS is most commonly used in commercial products, but insufficient for use in areas at high risk of infection.

One of the options for increasing the effectiveness of existing alcohol disinfection on small areas by spraying, and achieving full virucidal effect, is the addition of aldehydes (today most often a 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, bacterial resistance to glutaraldehyde has been identified and recent reports indicate that they cause severe asthma and other health problems.

A scientific article from the Brazilian Journal of Pharmaceutical Sciences, vol.45, n.2, abr./jun.,2009, mentions the minimum inhibitory concentrations (MICs) of disinfectants and / or stericizers, but does not mention glycolic acid or its disinfectant. effect.

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

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 a food, brewing or dairy production plant containing an inorganic acid (or mixture), an organic acid of 30 to 70%, e.g., glycolic acid or from 70 to 30% acetic acid, which is effective on Gram + and Gram- bacteria and yeast. It does not mention the use in medical and hospital facilities for disinfection of surfaces and surfaces, nor does it mention the effects on viruses, mycobacteria and TB strain.

SUMMARY OF THE INVENTION

It is an object of the present invention to use 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 ₈ -C ₆ -alkyl benzyl dimethyl ammonium chloride, C ₈ -C ₁₆ -alkyl dimethyl ammonium chloride and di (C ₈ -C ₁₆ -alkyl) dimethyl ammonium chloride, for disinfection, in particular for the disinfection of surfaces and medical devices.

SUMMARY OF THE INVENTION The present invention provides a disinfectant, particularly suitable for small areas, surfaces and medical devices, comprising glycolic acid, at least one C 1 -C 6 alcohol, and at least one quaternary ammonium compound selected from the group consisting of C ₈ -C 16 -alkyl benzyl dimethyl ammonium chloride, C ₈ -C ₆ -alkyl dimethyl ammonium chloride and di (C ₈ -C ₁₆ -alkyl) dimethyl ammonium chloride.

An advantage of the invention is to increase the microbial and virucidal efficacy of commercial products on the market and thereby extend the applicability of disinfection to areas of high risk of infection, without the need for problematic aldehydes. Surprisingly, it has been found that glycolic acid contributes to ensuring a full virucidal effect.

Preferably, the disinfectant composition comprises 50 to 88 wt. %, preferably 55 to 80 wt. % C | -C alcohol or a mixture of _Ci-C6 alcohols. Preferably, the C 1 -C ₆ 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 substances such as Bardac 22 and variously concentrated variants thereof, Bardac ®

LF, Barquat CB, Barquat DM, Barquat MB and Barquat BB (all from Lonza) or Protectol KLC50 (BASF).

In order to increase the microbial and virucidal activity, the preparation preferably contains 7 to 12 wt. %, more preferably 7 to 10 wt. %, glycolic acid.

The remainder to 100 wt. % of the disinfectant is water.

The formulation of the invention contains as one of the major antimicrobial components a C 1 -C 6 alcohol. The addition of quaternary ammonium compounds then potentiates the microbial effect of the alcohols and increases the effect against pathogenic fungi and enveloped viruses (e.g. HIV, HBV, etc.). In addition, it has good cleaning and wetting properties. The necessary glycolic acid content is required to ensure full virucidal activity.

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

The present invention further provides a method of disinfecting surfaces and medical devices, comprising the step of applying to the disinfected area or medical device 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 C ₈ -C ₁₆ -alkyl benzyl dimethyl ammonium chloride, C ₈ -C ₁₆ -alkyl dimethyl ammonium chloride and di (C ₈ -C ₁₆ -alkyl) dimethyl ammonium chloride.

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, resulting in a homogeneous, slightly yellowish solution that smelled of alcohols. The resulting pH is around 7.

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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 C | ₂ -C ₁₆ dimethylbenzylammonium chloride [g] 0.5 - - 0.5 1 - - C ₈ -C _l2 dimethylbenzyl ammonium 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 National Institute of Public Health in Prague and the accredited Chemila laboratory. The preparations were tested using both the suspension method and the disinfection method of contaminated carriers, which correspond to real conditions of use. The results are summarized in Table 1 below: Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values, Tab.

2: Results for the formulation of Example 6, and Table 3: Results for the formulation of Example 7.

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

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

The minimum inhibitory concentration (MIC), minimum bactericidal concentration at protein load at 10 min exposure (MBC-B), and minimum bactericidal concentration in aqueous solution at various exposures (MBC) are determined by the suspension micromethod.

b. The standard suspension method evaluates fungicidal (MFC - microscopic yeast fungi) and sporicidal (MSC) activity of substances in aqueous solution and protein load at various exposures and bactericidal activity (MBC) at different working solution temperature and protein load. (CSN EN 1650 (66 5203): Chemical disinfectants and antiseptics - Quantitative suspension test to determine fungicidal or anti-yeast chemical disinfectant activity * t

- 5 'preparations and antiseptics used in food, industry, household and public facilities Test method and requirements (Phase 2 / Grade 1)).

c. The artificially contaminated carrier method mimics the practical use of the products in immersion, wiping and spray disinfection. 25 x 25 mm glass or metal carriers are contaminated with a broth suspension of 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 in relation to the control fingerprints of non-disinfected carriers is evaluated.

The 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 Próteus vulgarit PrO 10/52 Serratia marcescens Srn 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 is 10 ^{8 '9} CFU / ml. (CFU - Coloniform Units).

Test samples are considered 100% and are diluted with sterile dest before use. water to the required concentration. To monitor the effect of protein substances on efficacy, samples are diluted with 20% bovine serum or nutrient broth. A decrease in CFU / ml by 5 to 6 orders is considered satisfactory.

A neutralizer is added to the culture medium: Tween 80 (3%), cysteine (0.1%), Lecithin (0.3%), sodium simatate (0.5%).

B. Evaluation of virucidal efficacy:

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 wiping, dipping or spraying, the efficacy of the preparation is evaluated by the plaque method.

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

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E.coli bacteriophage phi X 174 (NCTC 13706-B1 shown to 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 are diluted with sterile dest before use. water to the required concentration. 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

A modified suspension method where 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. The growth of fungi to sporulation in the blank on the surface of the liquid soil and the growth of colonies on the solid soil were evaluated.

The strains from the mycological culture collection of the Faculty of Science, 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 - Coloniform Units). A decrease in CFU / ml by 5 to 6 orders is considered satisfactory.

The percentages indicated correspond to the dilutions of the formulations of Example 6 and 6, respectively. 7, water.

Table 1: - MIC and MBC values

Composition according to example 6: Composition according to example 7: BALL 0,12% 0,12% MBC 3.3% 3.3%

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Table 2: Results for the formulation of Example 6

Microbe 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% / 5min. Pseudomonas aeruginosa 3.3% / 10 min. * netestováno Proteus vulgaris 3.3% / 10 min. * netestováno Seratia marcescens 3.3% / 10 min. * netestováno Candida albicans 100% -50% / 4 min. * 100% -50% / 5min. Aspergillus niger 100% - 50% / 5 min. * 100% - 50% / 5 min. Penicillium aurantiogriesum 100% -50% / 5min * 100% -50% / 5min. Mycobacterium terrae 100% / 5 min. * netestováno Mycobacterium avium 100% / 5 min. * netestováno E. coli bacteriophage Φ174 100% / 4 min. * 100% / 5 min.

* Protein tested

Table 3: Results for the formulation of Example 7

Microbe Suspension test Disinfection of contaminated carriers Min Concentration / Exposure Min Concentration / Exposure Staphylococcus aureus 3.3% / 10 min. * 100% -50% / 5min. Escherichia coli 3.3% / 10 min. * 100% -50% / 5min. Pseudomonas aeruginosa 3.3% / 10 min. * netestováno Proteus vulgaris 3.3% / 10 min. * netestováno Seratia marcescens 3.3% / 10 min. * netestováno Candida albicans 100% -50% / 4 min. * 100% - 50% / 5 min. Aspergillus niger 100% - 50% / 5 min. * 100% - 50% / 5 min. 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 effectiveness of three samples of disinfectants was compared:

Example 9: Alcohol

Example 10: 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, at 100% concentration of the preparation, with an exposure time of 5min.

Example Raw material 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

strain

10 11

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

‘9 Industrial applicability

The present composition can be used in liquid form on small areas by spraying with efficacy even on small non-enveloped viruses. It is used especially in highly endangered areas of infection, such as ICU, ARO, ambulance, ambulance, in 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)

Patent Claims' Use of 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 ₈ -C ₁₆ -alkyl benzyl dimethyl ammonium chloride, C ₈ -C ₁₆ -alkyl dimethyl ammonium chloride and di ( (C ₈ -C ₁₆ -alkyl) dimethyl ammonium chloride, for disinfection. Use according to claim 1, 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. % quaternary ammonium compound or mixtures of quaternary ammonium compounds, 7 to 12 wt. % glycolic acid. A disinfectant comprising glycolic acid, at least one C 1 -C ₆ alcohol, at least one quaternary ammonium compound selected from the group consisting of C ₈ -C ₁₆ -alkyl benzyl dimethyl ammonium chloride, C ₈ -C ₁₆ -alkyl dimethyl ammonium chloride and di (C ₈ -C ₁₆ -alkyl) dimethyl ammonium chloride. Disinfectant composition according to claim 3, characterized in that it contains 50 to 88 wt. % C _r C ₆ alcohol or a mixture of C-Co alcohol, 0.1 to 5 wt. % quaternary ammonium compound or mixtures of quaternary ammonium compounds, 7 to 12 wt. % glycolic acid and water. A disinfectant composition according to any one of claims 3 and 4, 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 of claims 3 to 5 is applied to the disinfected surface or medical device.