WO2007051957A1

WO2007051957A1 - Composition and method

Info

Publication number: WO2007051957A1
Application number: PCT/GB2006/002165
Authority: WO
Inventors: Keith Martin Macgregor
Original assignee: Ebiox Limited
Priority date: 2005-11-07
Filing date: 2006-06-14
Publication date: 2007-05-10
Also published as: EP1945274A1; GB0522655D0

Abstract

A sterilising composition comprising a source of peracetic acid, at least one anionic surfactant and at least one amphoteric surfactant. A method of using the composition to sterilise medical equipment is also described.

Description

COMPOSITION AND METHOD

The present invention relates to a composition and method for use in sterilising applications, particularly in the field of sterilising medical equipment.

It is essential that medical equipment is effectively sterilised between uses to prevent the spread of infection.

Many sterilising techniques rely on the use of high temperatures. However, some equipment may be heat- sensitive and become damaged if exposed to such harsh conditions .

An alternative sterilising method is immersion of equipment in a sterilising composition. Such compositions are well known.. However, they are often time-consuming to prepare, require long immersion periods, are unstable, or are of inadequate efficacy.

According to a first aspect of the present invention, there is provided a sterilising composition comprising a source of peracetic acid, at least one anionic surfactant and at least one amphoteric surfactant .

Preferably the sterilising solution is provided in concentrated form which may be diluted with water to form a sterilising solution.

The source of peracetic acid may comprise any suitable source. Preferably it comprises a peracetic acid precursor, and an activator. Preferably the peracetic acid precursor comprises an organic compound having at least one acetyl residue, preferably more than one acetyl residue.

The peracetic acid precursor compound preferably comprises an amine or alcohol having an acetyl group appended thereto i.e., preferably the peracetic acid precursor compound comprises an organic compound in which an acetyl group is bonded to a nitrogen or oxygen atom.

Preferably the peracetic acid precursor compound comprises an amine, preferably an amine having an acetyl residue bonded thereto. The peracetic acid precursor compound may comprise more than one amine group. At least one of said amine groups has an acetyl group appended thereto. Preferably there are at least two amine groups, each of which has an acetyl group appended thereto. In preferred embodiments the peracetic acid precursor compound comprises an organic compound having an amine group, said amine group having at least two acetyl groups bonded to a single nitrogen atom.

Most preferably the organic compound comprises a diamine. Preferably each nitrogen atom of said diamine has two acetyl groups appended thereto. Most preferably the peracetic acid precursor compound comprises tetraacetylethylene diamine. Alternatively, the peracetic acid precursor compound may be selected from the list comprising acetylsalicyclic acid, acetic acid, tetraacetyl glycouracil, pentaacetylglucose, N,N-diacetylaniline, N, N- diacetyl-p-toluidine; 1, 3-diacylated hydantoins, N- acylated cyclic hydrazides, and acylated triazones or urazoles . Suitable activators for use in the present invention include any means which may bring about the conversion of the peracetic acid precursor to peracetic acid.

Preferably the activator comprises an oxidising agent. Said oxidising agent is able to oxidise the acetyl groups on the peracetic acid precursor compound to form peracetic acid.

Suitable oxidising agents for use in the invention include alkali metal peroxides; hydrogen peroxide; organic peroxides, for example, urea peroxide, perbenzoic acid and peroxycarboxylic acids such as mono or diperoxyphthalic acid, diperoxy-azelaic acid, 2-octyldiperoxysuccinic acid, diperoxydodecanedicarboxylic acid, imidoperoxycarboxylic acid, the salts thereof, phlalimidoperhexanoic acid (PAP) ; and inorganic persalts, such as the alkali metal perborates, percarbonates , perphosphates , persilicates and persulfates .

Most preferably the activator comprises a perborate compound. In especially preferred embodiments the activator comprises sodium perborate, especially as a moήohydrate .

A preferred source of peracetic acid is tetraacetylethyl diamine as a peracetic acid precursor and sodium perborate monohydrate as an activator.

In any following definition which refers to the amount of a component present in a composition of the present invention, more than one of any such components may be present and the reference is made to the total amounts of all such components present in the composition.

The composition preferably comprises at least 20 wt% of the source of peracetic acid, more preferably at least

30 wt%, more preferably at least 40 wt%, most preferably at least 50 wt%.

The composition preferably comprises up to 90 wt% of the source of peracetic acid, more preferably up to 80 wt%, more preferably up to 75 wt%, most preferably up to 70 wt%.

The above percentages refer to the total amount of the source of peracetic acid, including the peracetic acid precursor and the activator.

Preferably the composition comprises at least 5 wt% peracetic acid precursor, more preferably at least 10 wt%, most preferably at least 12 wt%.

Preferably the composition comprises up to 40 wt% peracetic acid precursor, more preferably up to 30 wt%, most preferably up to 20 wt%.

Preferably the composition comprises at least 10 wt% activator, more preferably at least 20 wt%, more preferably at least 30 wt%, and most preferably at least

40 wt%.

Preferably the composition comprises up to 70 wt% activator, more preferably up to 60 wt%, more preferably up to 55 wt%, and most preferably up to 50 wt%. Preferably the composition comprises at least 0.1 wt% anionic surfactant, more preferably at least 0.5 wt%, more preferably at least 1 wt%, most preferably at least 1.5 wt%.

Preferably the composition comprises up to 10 wt% anionic surfactant, more preferably up to 8 wt%, most preferably up to 5 wt% anionic surfactant .

Suitable anionic surfactants include sodium and potassium salts of fatty carboxylic acids, sulfonates, alkyl sulfates, alkylether carboxylic acids and their salts, sulfosuccinates, alkoxylated alkyl sulfates, torides, alkylphosphates and sarcosocides .

Straight-chained or branched alkyl sulfates and alkyl polyalkoxylated sulfates, also known as alkyl ether sulfates may be produced by the sulfonation of higher C₈- C₂₀ fatty alcohols .

Examples of alkyl sulfate surfactants are those of formula:

ROSO₃ ^"M⁺

wherein R is a C₈-C₂₀ hydrocarbon group and M is a water- solubilising cation. Preferably R is Ci₀-C₁₆ alkyl, for example Ci₂-C₁₄, and M is an alkali metal such as lithium, sodium or potassium.

Examples of alkoxylated alkyl sulfates are ethoxylated alkyl sulfates of the formula: RO(C₂H₄O)_nSO₃-M⁺

wherein R is a C₈-C₂₀ alkyl group, preferably C₁₀-Ci₈ such as a Ci₂-Ci₆, n is at least 1, for example from 1 to 20, preferably 1 to 15, especially 1 to 6, and M is a salt- forming cation such as lithium, sodium, potassium, ammonium, alkylammonium or alkanolammonium.

The alkyl sulfates and alkyl ether sulfates may be used in the form of mixtures comprising varying alkyl chain lengths and, if present, varying degrees of alkoxylation.

Examples of other anionic surfactants which may be employed are salts of C₈-Ci₈ fatty acids, especially the sodium or potassium salts, and alkyl, for example C₈-Ci₈, benzene sulfonates .

Preferably the anionic surfactant comprises a sulfonate, more preferably an alkylbenzene sulfonate, most preferably a linear alkylbenzene sulfonate. In especially preferred embodiments said linear alkylbenzene sulfonate has between 8 and 18 carbon atoms. A suitable linear alkylbenzene sulfonate is commercially available under the trade mark Nansa HS80/S.

Preferably a composition of the present invention comprises at least 0.1 wt% amphoteric surfactant, more preferably at least 0.5 wt%, more preferably at least 1 wt%, most preferably at least 1.5 wt%. Preferably the composition comprises up to 10 wt% amphoteric surfactant, more preferably up to 8 wt%, most preferably up to 5 wt% amphoteric surfactant.

Suitable amphoteric surfactants include amphoteric betaine surfactant compounds having the following general formula:

R-N⁺(Ri)₂— R₂COO^"

wherein R is a hydrophobic group which is an alkyl group containing from 8 to 20 carbon atoms ; each R^ is an alkyl group independently containing from 1 to 3 carbon atoms; and R2 is an alkylene group containing from 1 to 6 carbon atoms .

Further exemplary useful amphoteric surfactants include those selected from alkylampho (mono) - and (di) - acetates, alkylampho (mono) - and (di) -propionates, and aminopropionates .

Exemplary alkylampho (mono) acetates include those according to the general structure:

wherein R represents a R represents a C8 to C24 alkyl moiety.

Alkylampho (di) acetates according to either of the general structures shown may be used:

wherein R represents a C8 to C24 alkyl moiety.

Suitable alkylampho (mono) propionates include those according to the according to the general structure :

wherein R represents a R represents a C8 to C24 alkyl moiety.

Suitable alkylampho (di) propionates include those according to either of the general structures :

wherein R represents a R represents a C8 to C24 alkyl moiety.

Suitable aminopropionates include those according to the following general structure : CH₂CH₂COO⁰ RNH⁹ CH₂CH₂COOH

wherein R represents a R represents a C8 to C24 moiety. In each of the above indicated structures, R represents a C8- C24 alkyl group and desirably is a C10-C16 alkyl group, especially derived from soy or coconut the latter of which typically provides a mixture of C8-10, C12, C14 and C16 alkyl groups .

Preferably the amphoteric surfactant comprises beta- alanine,N- (carboxyethyl) -N-dodecyl monosodium salt.

The mass ratio of anionic surfactant to amphoteric surfactant is preferably in the range of from 1:3 to 3:1. Preferably the anionic surfactant is present in a mass excess compared with the amphoteric surfactant. Most preferably the ratio of anionic surfactant to amphoteric surfactant is between 1:1 and 2:1, most preferably it is about 1.5:1.

Preferably the composition of the present invention further comprises a weak acid, preferably an organic acid.

Preferably, the composition of the present invention comprises a carboxylic acid having from 1 to 5 carbon atoms, and between 1 and 4 carboxylic acid residues. Most preferably the composition of the present invention comprises citric acid. Preferably the composition comprises said weak acid in an amount of at least 5 wt%, more preferably at least 10 wt%, most preferably at least 15 wt%.

Preferably the composition comprises up to 50 wt% weak acid, more preferably up to 40 wt%, most preferably up to 30 wt%.

Preferably the composition of the present invention further comprises one or more solubilising agents. Suitable solubilising agents include common salts of group 1 and group 2 metals .

Most preferably the solubilising agents are selected from the group consisting of sulfates, nitrates, carbonates and bicarbonates . Most preferably the composition of the present invention comprises sodium bicarbonate and sodium sulphate as solubilising agents .

Preferably the composition of the present invention further comprises a sequestrant. Suitable sequestrants include citrate, succinate, malonate, carboxymethyl succinate, carboxylate, polycarboxylate and polyacetyl carboxylate, as the salts of group 1 or group 2 metals, or as free acids .

Examples include the sodium, potassium and lithium salts of oxydisuccinic acid, mellitic acid, benzene polycarboxylie acids, Ci_O-C₂2 fatty acids and citric acid. Preferred sequestering agents are organic phosphonate type sequestering agents such as those sold by Monsanto under the trade mark Dequest, and alkylhydroxy phosphonates . A preferred sequestrant is phosphonic acid Deguest. The sequestering agent is preferably present in an amount of less than 1 wt%.

Preferably the composition of the present invention further comprises an indicator, most preferably a visual indicator. Preferably said indicator changes colour in the pH range of between 3 and 10, preferably of between 6 and 8. Suitable indicators include phenol red, brilliant yellow, cresol red, neutral red, paranitrophenol, and bromothymol blue. A preferred indicator is Phenol Red.

The indicator is preferably such that a colour change occurs when the useful life of a solution prepared from the composition of the present invention has expired.

The composition of the present invention is preferably provided as a powder. The above weight percentages of components present in the composition refer to this dry powder .

Suitably the composition is diluted to form a solution prior to use .

Preferably the composition of the present invention has a solubility at 40⁰C in water of at least 5g per litre, more preferably at least 1Og per litre, most preferably at least 15g per litre. Said solubilities are measured by stirring the composition in water at 40° C for a period of 5 minutes .

Preferably once dissolved the composition of the present invention forms an aqueous solution having pH of between 4 and 12, more preferably of between 2 and 11, more preferably between 5 and 11, preferably between 6 and 10, and most preferably between 7 and 9. In especially preferred embodiments the composition of the present invention forms a solution having an alkaline pH, preferably least 7.5. Most preferably the composition of the present invention provides a solution having an initial pH of about 8. The pH of the solution may vary over time, preferably the pH does not fall below 6 during the first 24 hours .

Preferably once dissolved the composition of the present invention forms a solution having a peracetic acid content of at least 900 ppm, after 5 minutes. More preferably at least 1,000, preferably at least 1,200 ppm, most preferably at least 1,400 ppm, after 5 minutes.

Preferably the composition of the present invention provides a solution which after 4 hours has a peracetic acid concentration of at least 700 ppm, more preferably at least 800 ppm, most preferably at least 1,000 ppm.

Preferably the composition of the present invention forms a solution which maintains a peracetic acid concentration of at least 700 ppm, more preferably at least 800 ppm, preferably at least 900 ppm, most preferably at least 1,000 ppm for at least 4 hours, more preferably at least 6 hours, more preferably at least 8 hours, and most preferably at least 10 hours.

In especially preferred embodiments the present invention provides a composition which dissolves to form a solution having a peracetic acid concentration of at least 1,400 ppm within 5 minutes, and which also maintains a peracetic acid concentration of at least 1,000 ppm over a period of 10 hours.

According to a second aspect of the present invention there is provided a concentrate composition comprising:

- 35 to 55 wt% sodium perborate monohydrate;

- 10 to 25 wt% tetraacetylethylene diamine;

- 2 to 5 wt% anionic surfactant;

- 1 to 3.5 wt% amphoteric surfactant .

According to a third aspect of the present invention there is provided a method of preparing a sterilising solution, comprising dissolving a composition of the first or second aspect in water at 40⁰C.

Preferably the method comprises dissolving between 10 and 3Og, most preferably between 18 and 22g, of the composition of the first or second aspect in 1 litre of water at 40 °C. Preferably the method further comprises allowing the temperature of the solution to fall to room temperature once dissolution is complete.

Preferably dissolution is complete after 10 minutes, more preferably after 5 minutes .

According to a fourth aspect of the present invention there is provided an aqueous sterilising solution comprising:

- 0.8 to 0.9 wt% sodium perborate monohydrate;

- 0.3 to 0.4 wt% tetraacetylethylene diamine; - 0.05 to 0.07 wt% anionic surfactant; and

- 0.04 to 0.05 wt% amphoteric surfactant.

According to a fifth aspect of the present invention there is provided a method of sterilising medical equipment, the method comprising the steps of :

(a) preparing a sterilising solution by dissolving a composition of the first or second aspect in water; and

(b) immersing the medical equipment in the sterilising solution for an appropriate period.

The appropriate period is the time necessary to inhibit or kill a significant portion of the microbes present on the medical equipment .

Preferably the appropriate period is at least 1 minute, more preferably at least 2 minutes, more preferably at least 3 minutes, most preferably at least 5 minutes.

Preferably the appropriate period is less than 4 hours, more preferably less than 3, more preferably less than 2 hours, most preferably less than 1 hour.

Preferably after the appropriate period, for example 5 minutes, at least 4.5 loglO of microbes present on the medical equipment prior to sterilisation are inhibited or destroyed, more preferably at least 5 loglO, more preferably at least 5.5 loglO, more preferably at least 6 loglO, most preferably at least 7 loglO. Preferably the composition of the present invention is active after the appropriate period, for example 5 minutes, against one or more of, and preferably all of, the following spores: Bacillus subtilis var niger and the following bacteria: Escheria coli, Mycobacterium tuberculosis, Staphylococcus aureus, Salmonella typhimurium, Pseudomonas aeruginosa, Campylobacter jejuni, Klebsiella aerogenes, Enterococcus faecium, Bacillus stearothermopohilus, Bacillus coagulans .

Preferably the composition of the present invention is active after the appropriate period, for example 5 minutes, against one or more of, and preferably all of, the following viruses: HIV, Adenovirus, Hepatitis B, Hepatitis C, Poliovirus, Cocksackievirus, Echovirus, Herpes simplex, Rotavirus. Preferably the composition of the present invention is active after the appropriate period, for example 5 minutes, against one or more of, and preferably both of, the following Fungi: Candida albicans, Aspergillus niger (spores) .

Preferably the sterilising method of the fifth aspect of the present invention may be carried out at room temperature .

Preferably the sterilising solution is prepared from the composition of the first or second aspect immediately prior to use. Suitably the composition may continue to be suitable for use for a period of at least 4 hours, more preferably at least 6 hours, more preferably at least 8 hours, most preferably at least 10 hours. Suitably when the composition will no longer be sufficiently active against microbes, there is a colour change of the sterilising solution.

The invention will now be further described by way of the way of the following non-limiting example.

Example

A composition was prepared having the following components :

3g sodium bicarbonate

44g sodium perborate monohydrate

17.5g tetraacetylethylene diamine

24g citric acid

3.5g Nansa HS80/S (linear alkylbenzene sulphonate)

2.4g Beta-alanine,N- (carboxyethyl) -N-dodecyl monosodium salt (AMA 100)

6.9g sodium sulphate

0.3g phosphonic acid Dequest 4266D

0.015g Phenol red

2Og of the above composition was dissolved in 1 litre of stirred water at 40⁰C. The concentration of peracetic acid present in the solution was measured at intervals of between 5 minutes and 24 hours. This was done by iodometric titration. The pH of the solution was also measured over these periods .

The solution was observed to gradually change colour from red to orange to yellow. In order to show that the solution could be prepared with reliable reproducibility, preparation as described above and the measurements taken were repeated 10 times. The results are shown in Tables 1 and 2 below.

Table 1

Table 2

Figure 1 shows a graph of the average peracetic acid release over the first 24 hours. These results clearly demonstrate that the present invention provides a reliable method of producing a composition having and a biocidally- effective concentration of peracetic acid for a prolonged period.

The composition has been independently evaluated by the Hospital Infection Research Laboratory (HIRL) , University of Birmingham, UK. HIRL found a reduction in colony forming units of > 6.5 loglO for Bacillus subtilis var niger spores in less than 2 minutes under clean and dirty conditions and a reduction of >5 loglO (5-8 loglO) c.f.u. for Mycobacterium tuberculosis in a clean and dirty carrier test with a contact time of 5 minutes .

Claims

1. A sterilising composition comprising a source of peracetic acid, at least one anionic surfactant and at least one amphoteric surfactant .

2. A sterilising composition according to claim 1 wherein the source of peracetic acid comprises a peracetic acid precursor and an activator.

3. A sterilising composition according to claim 2 wherein the peracetic acid precursor comprises tetraacetylethylene diamine .

4. A sterilising composition according to claims 2 or 3 wherein the activator comprises sodium tetraborate.

5. A sterilising composition according to any preceding claim wherein the anionic surfactant comprises a linear alkylbenzene sulfonate.

6. A sterilising composition according to any preceding claim wherein the amphoteric surfactant comprises beta- alanine,N- (carboxyethyl) -N-dodecyl monosodium salt.

7. A concentrate sterilising composition comprising:

- 35 to 55 wt% sodium perborate monohydrate ;

- 10 to 25 wt% tetraacetylethylene diamine;

- 2 to 5 wt% anionic surfactant;

- 1 to 3.5 wt% amphoteric surfactant .

8. A sterilising composition according to any preceding claim which further comprises citric acid.

9. A sterilising composition according to any preceding claim which further comprises a sequestering agent.

10. A sterilising composition according to any preceding claim which further comprises an indicator.

11. A sterilising composition according to claim 10 wherein the indicator is phenyl red.

12. A method of preparing a sterilising solution comprising dissolving a composition as claimed in any preceding claim in water at 40°C.

13. An aqueous sterilising solution comprising:

- 0.8 to 0.9 wt% sodium perborate monohydrate ;

- 0.3 to 0.4 wt% tetraacetylethylene diamine;

- 0.05 to 0.07 wt% anionic surfactant; and

- 0.04 to 0.06 wt% amphoteric surfactant.

14. A method of sterilising medical equipment, the method comprising the steps of :

15. A method as claimed in claim 14 wherein the appropriate period is between 5 minutes and 1 hour.

16. A method as claimed in claim 14 or claim 15 in which the method is carried out at room temperature.

17. A composition or method as hereinbefore described with reference to the examples .