CZ303941B6 - Disinfectant, process of its use and disinfection method - Google Patents

Abstract

In the present invention, there is described the use of a mixture of glycolic acid, at least one alcohol containing 1 to 6 carbon atoms, and at least one quaternary ammonium compound being selected from the group consisting of alkyl benzyl dimethyl ammonium chloride having 8 to 16 carbon atoms in the alkyl moiety, alkyl dimethyl ammonium chloride containing 8 to 16 carbon atoms in the alkyl moiety and dialkyl dimethyl ammonium chloride containing 8 to 16 carbon atoms in the dialkyl moiety, for disinfection. In the invention, there is further described a suitable disinfectant as well as process for disinfecting areas and sanitary means by applying the above-described 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 the disinfection of medical devices, carts, handles, handles, devices, etc. At these places the highest transmission of cerebrospinal infections occurs and therefore the high microbial effectiveness of the 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 dimethylammonium 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 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 existing alcohol disinfection on small areas by spraying, and by achieving full virucidal effect is the addition of aldehydes (today most often a combination of glutaraldehyde, glyoxal). Their use will be limited to glutaraldehyde in the future, 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.

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

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 production equipment in food, brewing or dairies containing inorganic acid (or mixture), organic acid in a content 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 hernia 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 Cg-C 1-6 alkyl. ₆ alkyl benzyl dimethyl ammonium chloride, C ₈ -C | _6- alkyl dimethyl ammonium chloride and di (C 5 -C ₁₆ alkyldimethyl ammonium chloride), for disinfection, in particular for disinfecting 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 _1-6 -alkyl benzyl dimethyl ammonium chloride, C ₈ -C ₁₆ -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 use of problematic aldehydes. Surprisingly, it has been found that glycolic acid contributes to ensure full virucidal effect.

Preferably, the disinfectant comprises 50 to 88 wt. %, preferably 55 to 80 wt. %, C1- _C6 alcohols or mixtures of C1- _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 agents 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 K.LC-50 (BASF) ).

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

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

The formulation of the invention contains as one of the major antimicrobial components a C 1 -C 6 alcohol. The addition of a quaternary ammonium compound then enhances 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 can be used in the disinfectant, in the case of the formation of a gel structure it is possible to incorporate gel-forming agents and associated suitable 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 ₈ -C _{8 6} alkyl benzyl dimethyl ammonium chloride, C ₆ -C ₈ -alkyl dimethyl ammonium chloride and di (C ₈ -C _b alkyl) dimethyl ammonium chloride.

-2GB 303941 B6

DETAILED DESCRIPTION OF THE INVENTION

Examples 1 to 7: Preparation and composition of disinfectants

All raw materials are in liquid form, cold water soluble. The raw materials were mixed at room temperature and the result was a homogeneous, slightly yellowish solution that smelled of alcohols. The resulting pH is around 7.

Example

Raw material

1 2 with 4 5 6 7 Ethanol [g] 45 45 80 45 - 1-Propanol [g] - - - - 45 45 55 2-propanol [gj 35 35 - 25 30 30 - Didecyldimethylammonium chloride [g] - - 1 - 1 and 1 C ₂ -C ₁₆ dimethylbenzylammonium chloride [g] 0.5 - - 0.5 1 - - C12-C8, ₈ -Dimethylbenzylammonium chloride [g] - 0.5 - - - - - Glycolic acid [g] 10 10 10 10 7 10 10 Water to iOOg

Example 8: Microbiological testing

The tests were carried out under the auspices of the National Institute of Public Health in Prague and the accredited laboratory Chemila. The preparations were tested by both the suspension method and the method of disinfection 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, Table 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

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. (EN 1650 (66 5203): Chemical disinfectants and antiseptics - Quantitative suspension test to determine fungicidal or anti-yeast activity

- J CZ 303941 Β6 chemical disinfectants and antiseptics used in food, industry, households and public facilities - Test method and requirements (phase 2 / step I)).

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 shown by imprinting the carriers on an agar plate and subsequently 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 Proteus vulgarit PrO 10/52 Serratia marcescens Sm 29/80 JF246 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 (CFU / ml) ATTC 9372

The density of the bacterial suspensions is 10 ⁸⁹ 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 thiosulphate (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 a virus suspension and, after disinfection by wiping, dipping or spraying, the efficacy of the preparation is evaluated by a plaque method.

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

E. coli bacteriophage phi X 174 (NCTC 13706 — Β1 detected on E.coli host (NCTC 13706/427/84

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

The virus suspension tested is 10 ^{7 8} PFU / ml. (PFU - plaque forming units).

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.

-4GB 303941 B6

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

A 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. The growth of fungi into 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 collection of cultures of Charles University, Prague are used for testing:

Aspergillus niger

Pemcillium 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%

Table 2: Results for the formulation of Example 6

Microbe Suspension test Disinfection of contaminated sites 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. * 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% / 5min * 100% -50% / 5min. Penicillium aurantiogriesum 100% -50% / 5min * 100% - 50% i 5 min. Mycobacterium terrae 100% / 5 min. * netestováno Mycobacterium avium 100% / 5 min. * netestováno E. coli bacteriophage Φ174 100% / 4 min. * i00% / 5min.

* Protein tested

- 5 GB 303941 B6

Table 3: Results for the formulation of Example 7

Microbe Suspension test Disinfection of contaminated sites 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. Pseudontonas 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% / 5min * 100% - 50% / 5 min. Penícillium aurantiogriesum 100% -50% / 5min * 100% -50% / 5min. 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 10: 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.

Example

Raw material

10 11

-propanol [g]

2-Propanol [g]

Didecyldimethylammonium chloride [g] Glycolic acid [g]

Water

45 45

25 30

1 to 100g to 100g to 100g

-6GB 303941 B6

Example strain

10 11

Staphylococcus aureus + Τ- 4- Escherichia coli Α 4- Candida albicans -4- + Aspergillus niger - / 15 min + 4- Penicillium aurantiogriesum - / 15 min + + E.coli bacíeriophage Φ174 - - +

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). 6-} alkyl) dimethyl ammonium chloride, for disinfection. Use according to claim 1, characterized in that the mixture contains 50 to 88 wt. %, 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. Third disinfectant composition characterized in that it contains glycolic acid, at least one C | -C ₆ alcohol, at least one quaternary ammonium compound selected from the group consisting of Cg-CI6-alkyl benzyl dimethyl ammonium chloride, Cr-C _1D alkyl dimethyl ammonium chloride and di (C ₈ -C ₆ -alkyl) dimethyl ammonium chloride. Disinfectant composition according to claim 3, characterized in that it contains 50 to 88 wt. %, 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 and water. The disinfectant composition of 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. -7EN 303941 B6 Method of disinfecting surfaces and medical devices, characterized in that a disinfectant composition according to any one of claims 3 to 5 is applied to the disinfected surface or medical device sc.