CA2165945C

CA2165945C - Cleaning and disinfecting formulations

Info

Publication number: CA2165945C
Application number: CA002165945A
Authority: CA
Inventors: Michel Pinoteau
Original assignee: Ecolab Inc
Current assignee: Ecolab Inc
Priority date: 1993-06-28
Filing date: 1994-06-20
Publication date: 2005-08-16
Anticipated expiration: 2014-06-20
Also published as: SK160995A3; CA2165945A1; SK280904B6; PL178201B1; DE59405533D1; EP0706556B1; DK0706556T3; ATE164389T1; TR27796A; ES2114204T3; PL312253A1; FR2708278A1; WO1995000613A1; FR2708278B1; EP0706556A1; CZ347795A3

Abstract

The invention concerns a cleaning and disinfecting agent containing a tertia ry alkylamine and an amine oxide, the ratio by weight of the tertiary alkylamine to the amine oxide being between 0.2 and 2. The agen t is diluted with water to a concentration at which it has a high antimicrobial and antimycotic action while at the same time ensuring a toxicity threshold which is acceptable to the user and ease of use in the disinfection of surfaces.

Description

~~ 65945 Cleaning and disinfecting formulations FIELD OF THE INVENTION
This invention relates to a cleaning and disinfect-ing formulation for disinfecting floors and walls, especially in hospitals, or for the antiseptic treatment of healthy skin.
BACKGROUND OF THE INVENTION
Nosocomial infections represent a major public health problem on account of their frequency, their potential seriousness and their economic and social consequences. They can be controlled by the application of efficient measures, for example by observing strict hygiene and disinfection procedures in various places, for example in the treatment of floors, walls and sur-faces of all kinds and in the treatment of surgical instruments and equipment.
The French Standards Committee AFNOR defines disin-fection as a process with a short-term outcome which enables microorganisms to be eliminated or destroyed and/or unwanted viruses present in contaminated neutral environments to be inactivated.
At the present time, the active substances most commonly used for disinfection in hospitals are alde-hydes, quaternary ammonium compounds and phenols. The aldehydes typically used for disinfection are formalde-hyde and glutaraldehyde. Although they have a particu-larly broad action spectrum, they are toxic both to users and to patients.
The inhalation of formaldehyde by human beings has a lachrymatory effect at concentrations above 0.1 ppm and causes irritation of the upper respiral=ory tracts with inflammation of the nasal, throat and :Larynx mucosa at concentrations of 1 to 5 ppm and lung oedema at concen-trations of 50 ppm. In hospitals, the use of relatively large quantities of formaldehyde in anatomy/pathology ~t.
..- .R.

laboratories and in haemodialysis units has caused acute poisoning. In addition, irritation of the eyes can occur in certain people exposed to formaldehyde in a concentra-tion above 0.4 ppm. In the event of local exposure of the mucosa, contact with formaldehyde can cause irrita-tion, changes in the cornea or eczema-like lesions..
After prolonged inhalation, glutaraldehyde can cause irritation of the respiratory organs in conjunction w:Lth coughing attacks in human beings. Where it acts locall;r on the mucosa, glutaraldehyde can cause irritation, erythema or changes in the cornea.
By virtue of their bactericidal and cleaning proper-ties, quaternary ammonium compounds are often used as disinfectants in hospitals. In human beings, however,, numerous cases of skin disease with contact allergies have been observed. Users who had used products based on quaternary ammonium either repeatedly or over prolonged periods showed oversensitivity reactions. The inhalation of mists or aerosols containing quaternary ammonium salt;
can result in lung oedema. Accordingly, there is a need to find a non-toxic cleaning and disinfecting formulation which could be used in hospitals instead of aldehydes and quaternary ammonium compounds.
The problem addressed by the present invention is to provide a new disinfecting and cleaning formulation which will not have any toxic effects on the user and which can readily be used for disinfecting surfaces.
THE SUMMARY OF THE INVENTION
The present invention relates to a cleaning and disinfecting formulation containing a tertiary alkylamine and an amine oxide in a ratio by weight of 0.2:1 to 2:1.
According to the invention, the active substance is an alkylamine with a bactericidal, fungicidal and~viruci dal effect. This substance is inhibited to only a very slight extent by the presence of interference substances.
In addition, it is completely safe both in toxicological terms and in ecological terms. It has been found to b~e of advantage to combine a synergistic quantity of an amine oxide with the above-mentioned alkylamine in order to obtain a significant increase in the antimicrobial effect in conjunction with a simultaneous cleaning effect. In one preferred embodiment of the invention designed to achieve maximum activity, the tertiary alkyl amine makes up from 2 to 15% by weight and preferab~-ly from 2 to 9% by weight of the composition as a whole.
The tertiary alkyl amine is preferably a compound corre-sponding to the following general formula:
/ (CH2)s-NH2 R~-N\
(CH2)s-NH2 in which R1 is an alkyl radical containing 8 to 16 and -preferably 10 to 14 carbon atoms. The amine oxide i:~
preferably a compound corresponding to the following general formula:
Hs R2-N.__-~O

in which R2 is an alkyl radical containing 8 to 16 and preferably 10 to 14 carbon atoms.
It has been found that the best results can be obtained when the radicals R1 and RZ are identical and, in particular, when Rl or RZ is a lauryl radical. In this case, the alkylamine is diaminopropyl laurylamine while the amine oxide is dimethyl laurylamine oxide.
In addition, the composition according to the invention may contain a low-foaming nonionic surfactant in a quantity of 2 to 20o by weight and preferably 2 to 13% by weight, based on the composition as a whole, and a fragrance in a quantity of 0 . 005 to 1 o by weight anct preferably 0.05 to 0.6% by weight, based on the compo:~i-tion as a whole. The nonionic surfactant may be an aliphatic polyalkoxyl derivative, for example a fatty alcohol ethylene oxide propylene oxide. It is preferably used in a ratio by weight of 0.2:1 to 4:1 to the alkylamine or the amine oxide.

DETAILED DESCRIPTION OF THE INVENTION
The present invention may best be described in ter_m:~
of the following preferred composition according to r_he invention which was found to show high activity:
Diaminopropyl laurylamine 5.40 Dimethyl laurylamine oxide 6%
Polyalkoxyl derivative 8%
Fragrance 0.1%
Aqueous auxiliaries qsf 100 The composition mentioned above is prepared in a TM
mixer into which purified water (Aqua purificata) , the dimethyl laurylamine oxide, the diaminopropyl laurylamine and the polyalkoxyl derivative are introduced while shaking in the order shown.
For the purposes of end use, the composition is diluted with water in a ratio of 20 ml of solution to 8 liters of water which corresponds to an in-use concentra-tion of 0.25%. The product according to the invention is a clear, amber-colored solution with a pH value of 1.1.2 ~ 0.5. It may be packed, for example, either in 20 m.l bags or in 5 liter canisters. By virtue of its anti~sep-tic effect and its non-toxicity according to the AFNOR
Standards, which will be discussed hereinafter, the composition according to the invention may be used fc>r the antiseptic treatment of healthy skin.
The antimicrobial effect of the preferred composi-tion according to the invention (above-cited example) was demonstrated in accordance with the AFNOR Standards. The results attached as appendixes relate to the variouas tests carried out by the membrane filter method. These 5 tests involved the following determinations:
- determination of the bactericidal effect in accord-ance with AFNOR NF T 72-151 (Appendix 1), - determination of the bactericidal effect in the presence of an interference substance (hard water) in accordance with AfNOR NF T 72-171 (Appendix 2), - determination of the bactericidal effect in the presence of an interference substance (albumin) in accordance with AfNOR NF T 72-171 (Appendix 3), - determination of the fungicidal effect in accordance with AfNOR NF T 72-201 (Appendix 4).
The bactericidal effect of the formulation was also TM
tested against Mycobacterium Tuberculosis by the Bactec TM
TB method. The Bactec TB Medium (12B) is a nutrient TM
medium based on enriched Middelbrook 7H9. The mycobac-teria use a carbon-14-labeled fatty acid present in the medium and give off COZ to the air.
If mycobacterial growth is present in the 12B
TM
bottles, the Bactec 460 measures the radioactivity caused by the 14 C02 released and displays it numerically on a scale of 0 to 999. These values are known as the growth index (GI). The increase in the GI is proportional to the bacterial count. After the Mycobacterium Tuber-culosis suspension has been exposed to the disinfectant, the mycobacteria remaining are counted by injecting each diluted germ suspension into two 12B bottles for several dilutions. The increase in the GI corresponds to the presence of mycobacteria.
TM
The method in question comprises using a McFarland 3 suspension in sterile distilled water which is prepared from a pure culture of Mycobacterium Tuberculosis taken TM
from a Lowenstein nutrient medium. Dilutions are pre-pared from this "mother" solution progressively by a factor of 10 up to a factor 109. 100 ~1 of each dilution are inoculated into a 12B medium containing 3 ml of culture medium (dilution 1/40 in each 12B bottle). 200 ~.l of pure or dilute disinfectant are then contacted with TM
200 ~,1 of Mycobacterium Tuberculosis with McFarland 3 over a certain period in a shaken 35 ml centrifuge tube.
After the contact time, the tube is filled with sterile distilled water and then centrifuged for 30 minutes. at 3000 r.p.m.. The supernatant phase is siphoned off and the residue is taken up in 2 ml of distilled water (dilu-tion 1/10 up to 10-5). The substance is then poured into two 12B bottles containing 4 ml of nutrient solution»
100 ~1 of the l0 1 dilution (dilution 1/40) 100 ~1 of the 10-2 dilution 100 ~tl of the 10 3 dilution 100 ~1 of the 10-4 dilution 100 ~1 of the 10-5 dilution TM
The count and the test are read off from the Bactec TB reader. The results expressed as the GI are set out in the Tables appearing in Appendix 5 for the individual contact times, being read off after double inoculation of the 12B nutrient media at the times T1, T2, T3, T6, T7, T8, T10, T13, T15, T16, T17 and T20. The toxicological studies carried out with the preferred composition according to the invention as defined above produced the following results:
a) Acute toxicity in male mice after oral administra-tion - LD50 > 2.5 ml/kg b) Index of acute eye irritation - 9.3 to 24 hours (product with mild irritant effect) c) Index of primary skin irritation - 0.71 (product with mild irritant effect) d) Index of primary skin irritation of the product in the in-use concentration (dilution to 0.25%) - 0.25 (product with no irritant effect) E x a m p 1 a s Appendix 1 Determination of bactericidal activity:
Standard AFNOR T 72-151, November 1987 I. Sample data:
Product designation and , batch number: Cleaning and disinfecting formulation for floors and surfaces Manufacturer: PARAGERM
Analysis period: May 1993 Active substances and concentrations: Confidentially disclosed II. Test conditions:
Test temperature: 20°C
Diluent used in the tests: Sterile distilled water III. Procedure determined after the preliminary test:
Type of membranes and data: Millipore filter Type HA, pore size 0.45 Rinsing liquid Composition - polysorbate 3%
- lecithin 0.3%
- histidine 0.1%
- sodium thiosulfate 0.5%
Number of rinses with this liquid: 3 Volume used for each rinse: 50 ml Neutralizing agent added to the counting medium and concentration:
Neutralizing nutrient medium for counting Composition:
beef extract 3 g tryptic casein peptone 5 g glucose 1 g lecithin 1 g polysorbate 7 g agar agar in powder form 15 g distilled water 1000 ml Determination of product:
of the bactericidal the activity Results of the preliminary tests under the descr ibed conditions Tested Strains, Collection Colonies Counted Concentrations and Number in the of the Product Collection N N~

n (V/V) 0.125% Pseudomonas aeruginosa 163 153 121 0.25% Escherichia coli 125 84 8 0.25% Staphylococcus aureus 132 124 130 0.25% Enterococcus hirae 85 94 65 0.25% Mycobacterium smegmatis 127 75 70 Results of the actual tests under the described conditions Colonies counted (+ = more than 150 colonies) Concentration of S T R A I N S N N' n the product in 50 contact with the to bacteria 150 pH (% V/V) Min. Max. 0.06% 0.125% 0.25%
*Pseudomonas aeruginosa 163 151 121 6.10 6.40 2 0 *Escherichia _ Coll 125 84 80 6.10 6.40 12 1 *Staphylococcus aureus 132 124 30 6.10 6.40 0 0 0 *Enterococcus hirae 85 94 65 6.10 6.40 0 0 0 *Mycobacterium smegmatis 127 75 50 6.10 6.40 0 0 Bactericidal concentration of the tested product in relation to:
Pseudomonas aeruginosa S 0.06%
Escherichia coli 5 0.06%
Staphylococcus aureus <_ 0.06%
Enterococcus hirae 5 0.06%
Mycobacterium smegmatis 5 0.125%
Based on all the strains tested, the product corresponds to the Standard AFNOR T 72-151 in a concentration of 0.125%.

Appendix 2 Determination of bactericidal activity in the presence of interference substances Standard AFNOR T 72-171 I. Salmple da Product designation and batch number: Cleaning and disinfecting formulation for floors and surfaces Manufacturer: PARAGERM
Analysis period: May 1993 Active substances and concentrations: Confidentially disclosed II. Test conditions:
Test temperature: 20°C
Diluent used in the tests: Sterile distilled water Interference substances: Hard water III. Procedure determined after the preliminarv test-Type of membranes and data: Millipore filter Type HA, pore size 0.45 a Rinsing liquid Composition - polysorbate 3%
- lecithin 0.3%
- histidine 0.1%
- sodium thiosulfate 0.5%
Number of rinses with this liquid: 3 Volume used for each rinse: 50 ml Neutralizing agent added to the counting medium and concentration:
Neutralizing nutrient medium for counting Composition:
beef extract 3 g tryptic casein peptone 5 g glucose 1 g lecithin 1 g polysorbate 7 g agar agar in powder form 15 g distilled water 1000 ml Determina tion of the bactericidal ivity of product:
act the Results of preliminary tests under the described the conditions Tested Strains, Collection Colonies Counted Concentrationsand Number in the of the ProductCollection N N' n (V/V) 0.5% Pseudomonas aeruginosa 62 61 58 0.25% Escherichia coli 147 126 108 0.25% Staphylococcus aureus 97 104 100 0.5% Enterococcus hirae 72 92 89 Mycobacterium smegmatis Results of the actual tests under the described conditions Colonies counted (+ = more than 150 colonies) Concentration of S T R A I N S N N' n the product in 50 contact with the to bacteria 150 pH (% V/V) Min. Max. 0.125% 0.25% 0.5%
*Pseudomonas aeruginosa 62 61 58 6.20 8.10 + 53 *Escherichia coli 147 126 108 6.40 6.20 0 0 *Staphylococcus aureus 97 104 100 6.40 6.70 0 0 *Enterococcus hirae 72 92 89 6.70 8.10 0 0 0 *Mycobacterium smegmatis Bactericidal concentration of the tested product in relation to:
Pseudomonas aeruginosa <_ 0.5%
Escherichia coli 5 0.125%
Staphylococcus aureus S 0.125%
Enterococcus hirae 5 0.125%
Mycobacterium smegmatis <_ Based on all the strains tested, the product corresponds to the Standard AFNOR T 72-171 in a concentration of 0.5% in the presence of hard water.

appendix 3 Determination of bactericidal activity in the presence of interference substances Standard AFNOR T 72-171 I. Sample da Product designation and batch number: Cleaning and disinfecting formulation for floors and surfaces Manufacturer: PARAGERM
Analysis period: May 1993 Active substances and concentrations: Confidentially disclosed II. Test conditions:
Test temperature: 20°C
Diluent used in the tests: Sterile distilled water Interference substances: Albumin - yeast extract III. Procedure determined after the preliminary test~
Type of membranes and data: Millipore filter Type HA, pore size 0.45 ~, Rinsing liquid Composition - polysorbate 3%
- lecithin 0.3%
- histidine 0.1%
- sodium thiosulfate 0.5%
Number of rinses with this liquid: 3 Volume used for each rinse: 50 ml Neutralizing agent added to the counting medium and concentration:
Neutralizing nutrient medium for counting Composition:
beef extract 3 g tryptic casein peptone 5 g glucose 1 g lecithin 1 g polysorbate 7 g agar agar in powder form 15 g distilled water 1000 ml Determina tion of the bactericidal ivity of the product:
act Results of the preliminary tests under the descr ibed conditions Tested Strains, Collection Colonies Counted Concentrations and Number in the of the Product Collection N N' n (V/V) 0.5% Pseudomonas aeruginosa 172 186 163 0.5% Escherichia coli 90 64 68 0.5% Staphylococcus aureus 53 56 53 0.5% Enterococcus hirae 102 101 109 Mycobacterium smegmatis 'WO 95/00613 16 PCT/EP94/02002 Results of the actual tests under the described conditions Colonies counted (+ = more than 150 colonies) Concentration of S T R A I N S N N' n the product in 50 contact with the to bacteria 150 pH (% V/V) Min. Max. 0.25% 0.5%
*Pseudomonas aeruginosa 172 186 163 6.70 8 *Escherichia Coli 90 64 68 6.70 0 *Staphylococcus aureus 53 56 53 6.70 26 *Enterococcus hirae 102 101 109 6.70 95 *Mycobacterium smegmatis Bactericidal concentration of the tested product in relation to:
Pseudomonas aeruginosa <_ 0.5%
Escherichia coli _< 0.5%
Staphylococcus aureus 5 0.5%
Mycobacterium smegmatis <_ Based on all the strains tested, the product corresponds to the Standard AFNOR T 72-171 in a concentration of 0.5%.

Appendix 4 Determination of fungicidal activity:
Standard AFNOR T 72-201, September 1987 I. Sample data:
Product designation and batch number: Cleaning and disinfecting formulation for floors and surfaces, filtration Manufacturer: PARAGERM
Analysis period: May 1993 Active substances and concentrations: Confidentially disclosed II. Test conditions:
Test temperature: 20°C
Diluent used in the tests: Sterile distilled water III. Procedure determined after the preliminary test' Type of membranes and data: Millipore filter Type HA, pore size 0.45 Rinsing liquid Composition - polysorbate 3%
- lecithin 0.3%
- histidine 0.1%
- sodium thiosulfate 0.5%
Number of rinses with this liquid: 3 Volume used for each rinse: 50 ml Neutralizing agent added to the counting medium and concentration: not applicable WO 95/00613 18 PCT/EP9~/02002 Results of the preliminary tests under the described conditions Tested Strains, Collection Colonies Counted Concentrations and Number in the of the Product Collection N N' n (v/v) Penicillinum verrucosum var.
cyclopium IP 1231-80 = LCP 282 Cladosporium cladosporioides IP 1232-80 = LCP 484 Absidia corymbifera IP 1129-75 = LCP 1942 0.5% Candida albicans IP 1180-79 = LCP 409 =

Results of the actual tests under the described conditions Colonies counted (+ = more than 150 colonies) Concentration of S T R A I N S N N' n the product in 50 contact with the to bacteria 150 pH (% V/V) Min. Max. 0.06% 0.125%
*Penicillinum verrucosum *Cladosporium cladosporioides * Absidia corymbifera * Candida albicans 111 108 95 6.10 6.40 0 0 Fungicidal concentration of the tested product in relation to:
Penicillinum verrucosum: %
Cladosporium cladosporioides: %
Absidia corymbifera: %
Candida albicans: <_ 0.6%
Appendix 5 Strain: M. Tuberculosis tested without disinfectant From a McFarland 3 suspension of the strain, 100 ~1 of each dilution (10-1 to 10-5) are inoculated into a 12B bottle Tl T2 T3 T6 T7 T8 T10 T13 T15 T16 T17 T21 12th 13th 14th 17th 18th 19th 21st 24th 26th 27th 28th 1st May May May May May May May May May May May July 1 14 64 109 999 Pur. - - - - - - -2 1 8 14 175 204 314 999 Pur. - - - -Pur. - Purified Disinfectant for floors and surfaces diluted to 0 25% tested at 50% with M. Tuberculosis Contact time : 5 minutes with shakinct AK

12th 13th 14th 17th 18th 19th 21st 24th 26th 27th 28th 1st May May May May May May May May May May May July 1 0 0 0 68 88 124 398 999 Pur. - - -Pur. - Purified 'O 95/00613 20 PCT/EP94/02002 The M. Tuberculosis strain tested without disinfectant grew to 10-5 after culture for 15 days.
In the presence of the 0.25% disinfectant, growth is observed at 10-4 after culture for 13 days.
No growth for the first few days with the 10-1 dilution.
Disinfectant for floors and surfaces diluted to 0.550 tested at 50% with M. Tuberculosis Contact time 5 minutes with ~~hakina AM

12th 13th 14th 17th 18th 19th 21st 24th 26th 27th 28th 1st May May May May May May May May May May May July - 0 0 0 74 94 135 474 999 Pur. - - -~ ~

Pur. - Purified The development is similar to that indicated i.n the previous Table.
It should be understood that the detailed description and specific examples which indicate the presently preferred embodiments of the invention are given by way of illustration only since various changes and modifications within the spirit and scope of the appended claims will become apparent to those of ordinary skill in the art upon review of the above description.

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A cleaning and disinfecting formulation, comprising a tertiary alkylamine and an amine oxide, wherein the ratio by weight of the tertiary alkylamine to the amine oxide is between 0.2:1 and 2:1, and wherein the tertiary alkylamine has the following formula:
and the amine oxide has the following formula:
and wherein R1 and R2 are alkyl radicals containing 8 to 1.6 carbon atoms.

2. The cleaning and disinfecting formulation of claim l, wherein R1 and R2 are alkyl radicals containing 10 to 14 carbon atoms.

3. The cleaning and disinfecting formulation of claim 1, in which the radicals R1 and R2 are identical.

4. The cleaning and disinfecting formulation of claim 3, wherein the tertiary alkylamine is diaminopropyl laurylamine and the amine oxide is dimethyl laurylamine oxide.

5. The cleaning and disinfecting formulation of claim 4 containing 2 to 15% by weight of diaminopropyl laurylamine, based on the composition as a whole.

6. The cleaning and disinfecting formulation of claim 5 further comprising a nonionic surfactant.

7. The cleaning and disinfecting formulation of claim 6, in which the nonionic surfactant is an aliphatic polyalkoxyl derivative.

8. The cleaning and disinfecting formulation of claim 7, in which the nonionic surfactant is a fatty alcohol ethylene oxide propylene oxide.

9. The cleaning and disinfecting formulation of claim 6, in which the nonionic surfactant is present in a ratio by weight of 0.2:1 to 4:1 to the tertiary alkylamine or t:he amine oxide.

10. The cleaning and disinfecting formulation of claim 7, in which the nonionic surfactant is present in a ratio by weight of 0.2:1 to 4:1 to the tertiary alkylamine or the amine oxide.

11. The cleaning and disinfecting formulation of claim 8, in which the nonionic surfactant is present in a ratio by weight of 0.2:1 to 4:1 to the tertiary alkylamine or the amine oxide.

12. The cleaning and disinfecting formulation of claim 1 further comprising a fragrance.

13. The cleaning and disinfecting formulation of claim 6 further comprising a fragrance.

14. The cleaning and disinfecting formulation of claim 13 which contains 2 to 20% by weight of nonionic surfactant and 0.05 to 1% by weight of fragrance, based on the composition as a whole.

15. The cleaning and disinfecting formulation of claim 14, wherein said formulation comprises the following constituents diluted with water:
Diaminopropyl laurylamine 5.4% by weight, Dimethyl laurylamine oxide 6% by weight, Polyalkoxyl derivative 8% by weight, Fragrance 0.1% by weight.