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Publication numberWO1994022305 A1
Publication typeApplication
Application numberPCT/EP1994/000821
Publication date13 Oct 1994
Filing date15 Mar 1994
Priority date1 Apr 1993
Publication numberPCT/1994/821, PCT/EP/1994/000821, PCT/EP/1994/00821, PCT/EP/94/000821, PCT/EP/94/00821, PCT/EP1994/000821, PCT/EP1994/00821, PCT/EP1994000821, PCT/EP199400821, PCT/EP94/000821, PCT/EP94/00821, PCT/EP94000821, PCT/EP9400821, WO 1994/022305 A1, WO 1994022305 A1, WO 1994022305A1, WO 9422305 A1, WO 9422305A1, WO-A1-1994022305, WO-A1-9422305, WO1994/022305A1, WO1994022305 A1, WO1994022305A1, WO9422305 A1, WO9422305A1
InventorsKathryn Bellamy, Robert Alcock, Kevin Leslie Laban, Ronald Archie Hudson
ApplicantUnilever N.V., Unilever Plc
Export CitationBiBTeX, EndNote, RefMan
External Links: Patentscope, Espacenet
Disinfectant compositions
WO 1994022305 A1
Abstract
There is provided an aqueous virucidal composition suitable as hospital disinfectant, comprising alkaline material and from 0.01 to 5 % by weight of an alkyl quaternary nitrogen salt, and having a pH in the range of 10-12. This composition was found to be effective for killing non-enveloped viruses such as polio viruses, and for disinfecting heat sensitive medical instruments, such as flexible endoscopes.
Claims  (OCR text may contain errors)
1. The use of an aqueous composition containing an alkaline material selected from alkali metal carbonates and alkali metal hydroxides, and from 0.01 to 5% by weight of an alkyl quaternary nitrogen salt, and having a pH in the range of from 10-12, as an anti-viral agent.
2. Use of the composition according to claim 1 for killing non-enveloped viruses, such as polio-viruses.
3. Use of the composition according to claim 1 for disin¬ fecting heat sensitive medical instruments, such as flexible endoscopes.
4. Aqueous virucidal composition suitable as hospital disinfectant, comprising alkaline material selected from alkali metal carbonates and alkali metal hydroxides, and from 0.01 to 5% by weight of an alkyl quaternary nitrogen salt, and having a pH in the range of 10-12.
5. Composition according to claim 4, wherein the quater¬ nary nitrogen salt comprises at least one compound of the formulas (I) or (II) :
wherein :
R2 is a saturated or unsaturated, branched or linear alkyl group having 10-18 carbon atoms;
R2, R3 and R4 are methyl, benzyl, substituted benzyl, or saturated or unsaturated, linear or branched alkyl groups having 10-18 carbon atoms; X" is a halide ion.
6. Composition according to claim 5, wherein the quaternary nitrogen salt comprises at least one quaternary ammonium halide of the formula (I) .
7. Composition according to claim 6, wherein the quaternary ammonium halide is a dialkyl quaternary ammonium halide.
8. Composition according to claim 6 or 7, wherein the quaternary ammonium halide contains a halide selected from the group consisting of chloride and bromide.
9. Composition according to any of claims 4-8, wherein the composition comprises from 0.02 to 1% by weight of the alkyl quaternary nitrogen salt.
10. Composition according to any of claims 4-9, wherein the composition comprises from 0.2 to 10% by weight of the alkaline material.
11. Composition according to any of claims 4-10, wherein the composition comprises from 10 to 30 % by weight of an alkanol selected from the group consisting of ethanol, iso- propanol and n-propanol.
*********
Description  (OCR text may contain errors)

DISINFECTANT COMPOSITIONS

FIELD OF THE INVENTION

The invention relates to disinfectant compositions. More specifically, it relates to aqueous disinfectant com¬ positions containing an alkyl quaternary nitrogen salt in the presence of an alkaline component.

The invention is particularly suitable to be used for disinfecting objects and surfaces at locations where con- tamination is of major concern, such as in hospitals, in the food and beverage industry and in the veterinary field.

PRIOR ART AND BACKGROUND OF THE INVENTION

It is known that compositions comprising a quaternary am- monium halide and a sodium carbonate can be effectively used as anti-bacterial disinfectants.

FR-A-2 229 426 (Reusse) discloses an anti-bacterial auto- biodegradable disinfectant composition comprising 0.1-0.2% by weight of a quaternary ammonium chloride and 35 -40% by weight of sodium carbonate.

DE-A- 2 512 835 (Milbradt) discloses a granular germicidal disinfecting hospital laundering composition comprising one or more quaternary ammonium compounds and sodium carbonate.

It is an object of the present invention to provide an anti-viral composition having low toxicity and low cor- rosivity.

It is a further object of the invention to provide an anti- viral composition which shows effective killing ability with respect to non-enveloped hydrophilic viruses, par¬ ticularly polio-viruses. It is another object of the inven¬ tion to provide an anti-viral composition which can be effectively applied as an hospital disinfectant. It was surprisingly found that these and other objects could be achieved with a composition according to the present invention. DEFINITION OF THE INVENTION

The present invention relates to the use of an aqueous com¬ position containing an alkaline material selected from alkali metal carbonates and alkali metal hydroxides, and from 0.01 to 5% by weight of an alkyl quaternary nitrogen salt, and having a pH in the range of from 10-12, as an anti-viral agent. Furthermore, the invention provides an aqueous virucidal composition suitable as hospital disin¬ fectants, comprising alkaline material selected from alkali metal carbonates and alkali metal hydroxides, and from 0.01 to 5% by weight of an alkyl quaternary nitrogen salt, and having a pH in the range of 10-12.

DETAILED DESCRIPTION OF THE INVENTION It is known that aqueous compositions containing alkyl quaternary nitrogen salts, particularly quaternary ammonium compounds exhibit some cleaning and bactericidal activity. However, a disadvantage of these compositions is that they are not able to inactivate uncoated viruses such as polio- viruses. It has now been found that addition of an alkaline material selected from alkali metal carbonates and hydroxides, to these compositions such that their pH is raised up to values in the range of 10-12, not only increases the disinfecting characteristics but also has a pronounced effect on the virucidal ability thereof.

In this context, an aqueous composition is defined to be a composition containing at least 90% water.

The use of the composition of the invention The aqueous composition of the invention was found to be very effective when used for killing non-enveloped viruses, in particular polio viruses. The effectiveness of the com¬ position was reduced when it was applied in the presence of serum, but this effect could be overcome by the addition of an alkanol solvent selected from the group of ethanol, isopropanol, and n-propanol. The product according to the invention is intended for use in high risk areas where contamination is of major concern, such as in human health care, veterinary health care and the food industry. The product is particularly suitable for use as disinfectant of medical instruments, especially of flexible endoscopes and similar heat-sensitive delicate instruments, that may be contaminated with viruses. The reason for this applicability of the product of the invention, is that both its toxicity and its aggressivity to delicate instruments are low.

The quaternary nitrogen salt

The alkyl quaternary nitrogen salt present in the aqueous virucidal composition of the invention may be selected from a broad range of compounds which contain at least one alkyl quaternary nitrogen group, and of which a common charac¬ teristic is their surface activity caused by the (at least one) alkyl group present therein. Particularly suitable compounds are ammonium salts, pyridiniu salts, and quinolinium salts.

Preferably, the quaternary nitrogen salt is selected from compounds of the formulas (I) or (II) :

wherein: R2 is a saturated or unsaturated, branched or linear alkyl group having 10-18 carbon atoms; R2, R3 and R4 are methyl, benzyl, substituted benzyl, or saturated or unsaturated, linear or branched alkyl groups having 10-18 carbon atoms; X~ is a halide ion.

The level of the alkyl quaternary nitrogen salt present in the aqueous virucidal composition is generally in the range of from 0.01 to 5% by weight, preferably from 0.02 to 1% by weight. Favourable results, particularly with regard to the virucidal activity on uncoated viruses, were found when at least one quaternary ammonium halide is contained in the composition of the invention, said halide being preferably a dialkyl quaternary ammonium halide. Furthermore, the halide in those quaternary ammonium compounds is desirably a chloride or a bromide.

The alkaline material

Generally, the level of the alkaline material in the com¬ position of the invention is to be such that the pH is in the range of from 10 to 12. Depending on the type of alkaline material, a suitable level of such material is in the range of from 0.2 to 10% by weight.

Generally alkali metal carbonates and hydroxides are ap¬ plied as alkaline material in the composition of the inven- tion. Preferred types of alkaline material for use in the composition of the invention, are sodium carbonate and sodium hydroxide, for reasons of availability.

Anti-viral activity It is an essential feature of the disinfectant compositions of the invention that the incorporation of an alkaline salt into a disinfectant containing a surface active quaternary nitrogen compound should bring about an improvement of the anti-viral activity. The anti-viral activity of various disinfectant compositions on the polio-virus is assessed using the DW test, as described in Bundesgesundheits Blatt 25 No 12, 1982, p.297. The alkanol solvent

The alkanol solvent is not only suitable for restoring the effectiveness of the virucidal composition when applied in the presence of a serum. It can also be effectively applied for avoiding inactivation of the virucidal composition of the invention by organic soil. Suitable types of alkanol compounds are in this respect ethanol, iso-propanol and n- propanol. The alkanol is preferably present in an amount of from 10 to 30% by weight of the virucidal composition.

The invention will be further illustrated by the following non-limiting examples wherein parts and percentages are by weight, unless otherwise indicated.

In these examples the following abbreviations are used: BARDAC 22 : dialkyl dimethyl quaternary ammonium chloride (50% active),ex Lonza Na C03 : sodium carbonate

K2C03 : potassium carbonate

Comparative Examples A.B

For the purpose of comparison, the virucidal activity of two different demineralised aqueous disinfectant solutions of BARDAC 22 against the polio-virus type 1 (Mahoney strain) , was tested as follows.

Suspension tests were carried out according to the guidelines of the Deutsche Vereinigung zur Bekampfung der Viruskrankheiten (published in: Hygiene and Medicine 9., 177-179 (1984)). The polio-virus was obtained from Natec, Hamburg, and Vero cells (Green Monkey Kidney) were pur¬ chased from Flow Laboratories.

The polio-virus was grown in confluent layers of Vero until complete cytophatic effect was observed. Cultures were then frozen and thawed, after which they were centrifuged to remove cell debris. The supernatant was stored in aliquots at -70 °C. The virus content of the suspension was deter¬ mined by titration.

Monolayers of Vero cells were cultured in 96 well microtitre plates in a 5% carbon dioxide atmosphere. Ten¬ fold dilutions of virus suspension were made in maintenance medium. One hundred microlitres of each dilution were added to a single well, five replicates of each dilution were made. Cell controls were included on every plate. The plates were incubated at 37 °C in a C02 incubator, observed daily and discarded after seven days. The virus titre was calculated from the Karber formula (Lenette E.H. and Schmidt N.J. , Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections, 5th Edition, p.32-35 (1979)).

The suspension tests were carried out at room temperature (20 °C) but, after appropriate contact times of respectively 2 and 5 minutes, dilutions were made in ice- cold medium.

Two suspensions of viruses having known titres of 6.7 and

6.3 as calculated using the Karber formula

(log10 TCID50/0.1 ml: log10 of 50% tissue culture infectuous dose, per 0.1 ml), were used for the tests.

One volume of virus suspension was mixed with one volume of distilled water and eight volumes of aqueous disinfectant solution. The mixture was kept at 20 °C for the duration of the contact time applied.

After appropriate contact times, samples were taken and an initial 1:100 dilution was made by adding 0.1 ml to 9.9 ml medium, subsequent dilutions being made by adding o.l ml to 0.9 ml. All dilutions were made in ice-cold medium, and the tubes containing the dilutions were kept on ice until they were inoculated into cell cultures. One hundred microlitres per well, 5 replicates for each dilution. The micro-titre plates were incubated at 37 °C in an in¬ cubator with a 5% C02 atmosphere, and examined daily until they were discarded on day 7. The polio virus titre for each contact time was calculated as before using the Karber formula. The following results from these suspension tests were found.

Example aα.disinfect. solution Virus titre recovered

No. contacted after contact time of 2 in. 5 min.

A 0.2 %wt sol. of BARDAC 22 6.5 5.9

B 0.05 %wt sol. of BARDAC 22 6.1 6.5

Examples 1-4

Several anti-viral disinfectant compositions according to the present invention were formulated, said compositions being demineralised aqueous solutions containing BARDAC 22 and sodium or potassium carbonate.

The virucidal activity of these aqueous solutions against the polio-virus type 1 (Mahoney strain) , was tested fol¬ lowing the procedure of the suspension test described in Examples A and B. The following results expressed in polio virus titres recovered after the appropriate contact times, and calculated using the Karber formula, were obtained.

Example A . disinf. solution Virus titre recovered No. including; after contact time of

2 min. 5 min.

1 0.2% BARDAC 22 + 0.2% Na2C03 < 2.5 < 2.5 2 0.05% BARDAC 22 + 0.2% Na2C03 < 2.5 < 2.5 3 0.2% BARDAC 22 + 0.2% K2C03 < 2.5 < 2.5 4 0.05% BARDAC 22 + 0.2% K2C03 < 2.5 < 2.5 When comparing Examples 1-4 with Comparative Examples A,B , it can be concluded that, at both contact times applied, the aqueous disinfectant solutions of the invention and containing both BARDAC 22 and an alkali metal carbonate achieved a reduction of about 4 in the virus titre, as com¬ pared to the test results of the comparative disinfectant solutions containing only BARDAC 22.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
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DE4005784A1 *23 Feb 199029 Aug 1991Schuelke & Mayr GmbhDisinfectant concentrates effective against mycobacteria and viruses - contg. phenoxy-ethanol or -propanol, guanidinium or quat. ammonium cpd., nonionic surfactant, and N-base as synergist
EP0190797A2 *30 Jan 198613 Aug 1986John Kenneth VoitMethod for killing viruses and composition therefor
FR2139074A1 * Title not available
US3941696 *24 Mar 19752 Mar 1976Baylor College Of MedicineSterilization of holding tanks and toilet bowls by quaternary compounds
Non-Patent Citations
Reference
1 *CHEMICAL ABSTRACTS, vol. 119, no. 19, 8 November 1993, Columbus, Ohio, US; abstract no. 195159q, M. KAGEYAMA ET AL.: "Inactivation activity of various disinfectants against infectious bursal disease virus"
2 *CHIKUSAN NO KENKYU, vol. 47, no. 8, 1993, pages 929 - 931
Referenced by
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WO1998009660A1 *6 Sep 199612 Mar 1998Epic Therapeutics, Inc.Viral inactivation of biological fluids with biomolecule activity retention
WO2003041747A1 *8 Nov 200222 May 2003Biotec Global LimitedComposition, method and apparatus for sterilisation of medical instruments
WO2003059062A1 *16 Jan 200324 Jul 2003Lonza AgVirucidal disinfectant
WO2009074330A1 *11 Dec 200818 Jun 2009Bundesrepublik Deutschland Vertreten Durch Das Bundesministerium Für Gesundheit Und Soziale Sicherung Letztvertreten Durch Den Präsidenten Des Robert-Koch-InstitutsA formulation for broad-range disinfection including prion decontamination
DE102005006104A1 *10 Feb 200524 Aug 2006Merz Pharma Gmbh & Co. KgaaAqueous based agents, useful as e.g. cosmetic disinfectant and cleaner, comprises inorganic alkali- and/or alkaline- earth salts, monovalent alcohols, cationic surfactants and optionally additives and/or auxiliary materials
US5932468 *1 Nov 19963 Aug 1999Grupo Grifols, S.A.Method of inactivating viruses in proteins
US707115230 May 20034 Jul 2006Steris Inc.Cleaning and decontamination formula for surfaces contaminated with prion-infected material
US71290804 Oct 200231 Oct 2006Steris Inc.Vitro model of priocidal activity
US72176859 May 200615 May 2007Steris Inc.Cleaning and decontamination formula for surfaces contaminated with prion-infected material
US73938183 Apr 20071 Jul 2008Steris Inc.Cleaning and decontamination formula for surfaces contaminated with prion-infected material
US7803315 *3 Apr 200228 Sep 2010American Sterilizer CompanyDecontamination of surfaces contaminated with prion-infected material with gaseous oxidizing agents
US822173316 Jan 200317 Jul 2012Lonza AgVirucidal disinfectant
Classifications
International ClassificationA01N43/40, A01N33/12
Cooperative ClassificationA01N43/40, A01N33/12
European ClassificationA01N33/12, A01N43/40
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