A DISINFECTANT FORMULATION
Field of the Invention
The present invention relates to a disinfectant system for use, for example, in human and animal health applications. The system contemplates in-situ generation of an organic peroxyacid to function as disinfectant.
Background to the Invention
Disinfectants are becoming more widely used in an increasing number of industries. Amongst the reasons for the increasing use is the need to comply with more stringent Health and Safety Regulations as well as the fact that the number of organisms resistant to certain disinfectants is increasing. Much research in this technical area is concerned with finding more active means of disinfection, usually chemical. Amongst the problems with such active chemical disinfectants, one which is particularly difficult to overcome is the long-term stability of the disinfectant. Often the chemical groups of a molecule which make it an effective disinfectant, are the groups which make the molecule inherently unstable.
One class of molecules which is widely recognised as including fairly aggressive disinfectants, is that of the organic peroxyacids. In recent years research has been directed at these compounds, aimed not least in providing a stable and safe means of their delivery. Amongst the peroxyacids, the one which has been the subject of closest attention has been peroxyacetic acid (often referred to as peroxyacetic acid or PAA). This particular peroxyacid is rarely isolated and is normally encountered in solution in both aqueous and non-aqueous media. Peroxyacetic acid is often supplied as an equilibrium mixture including primarily water, acetic
acid and hydrogen peroxide, together with a number of other minor components such as stabilisers. However, even equilibrium systems of peroxyacetic acid are inherently thermodynamically unstable due to the decomposition of peroxyacetic acid into acetic acid and oxygen. Such decomposition can be slowed down if special measures are taken but cannot be completely prevented.
A further property of peroxyacids which makes them difficult to use or store is that they can decompose rapidly and violently, particularly peroxyacids of low molecular weight and of high purity.
Because of the above it is often difficult to provide a particular concentration of peroxyacid required. In order to get around this problem, peroxyacids are often generated in-situ to perform the particular desired function. Such in-situ generation has advantages in that the amount of peroxyacid produced can be controlled through control of the starting materials and also the consumption of starting materials is optimised. Moreover, higher concentrations of peroxyacid can be achieved than are available from equilibrium systems due to the non- equilibrium nature of the in-situ systems.
Typically, in order to generate the peroxyacid, a peroxyacid precursor is reacted with a peroxide source, usually hydrogen peroxide. As examples of peroxyacid precursors (often referred to as activators), molecules containing groups such as amides (including lactams), acyl halides, or esters - particularly gem-diesters, but also including lactones - can be named. Such a system, as indicated above, will normally not be in an equilibrium state and the rate of peroxyacid generation will depend on, amongst other things, the concentration of the reactants and their reactivity.
However, it is often necessary, particularly if rapid generation of the peroxyacid is required, to have one or more of the reactants present in excess. Apart from being wasteful, this can lead to increased hazards, especially where high concentrations of hydrogen peroxide are present. Higher concentrations of hydrogen peroxide are not only intrinsically unsafe in themselves, but attract a more severe chemical hazard rating which has implications for the packaging and the transport of material.
It is therefore of advantage to supply a system which provides in-situ peracid generation with the use of hydrogen peroxide at lower concentrations of the hydrogen peroxide. The invention described below seeks to address the above problems.
Summary of the Invention
According to the invention there is provided a method of production of a solution containing a peroxyacid, the method including the steps of mixing together a first and second aqueous solution; the first solution having a pH of from 7 to 9.5 and comprising;
hydrogen peroxide at a concentration of up to 8% w/w;
an alkali metal borate salt at a concentration of up to 5% w/w
a peroxide stabiliser; the second solution comprising;
an activator reactable with hydrogen peroxide to form a peroxyacid;
a structuring electrolyte; and
a surfactant;
the second solution having a pH of from 6 to 10;
the first and second solutions being mixed together in water in a ratio of from 1 :100 - 100:1 by weight of the first solution to the second solution.
The solution thus provided, yields the peroxyacid rapidly at the desired concentration for the particular disinfection treatment being undertaken.
The structuring electrolyte is preferably citric acid or an alkali metal salt thereof and is present in sufficient quantity to maintain the activator, where solid in
suspension. Levels of structuring electrolyte of 7-12% w/w of the second solution have been found to be particularly suitable and preferably of 9-11% w/w.
The borate salt is advantageously a tetraborate and preferably has a concentration of less than 4% w/w of the first solution.
The surfactant can advantageously be a nonionic or an anionic surfactant or a mixture thereof. The nonionic surfactant is particularly advantageously a fattyalcoholethoxylate or polyethoxylate with preferably 12-15 carbon atoms in the chain. The anionic surfactant is particularly advantageously an organosulphonic acid or salt thereof such as an alkylbenzenesulphonate, for example dodecylbenzenesulphonic acid.
Preferably the peroxide stabiliser is added at a level sufficient to sequester peroxide decomposition catalysts, for example, transition metal ions such as iron
(II), or iron (III). Typical levels of stabiliser are from 0.3 to 0.6% w/w of the first solution. The stabiliser can be chosen from one or more of groups well known in the art such as phosphates, organophosphonic acids, carboxylic acids or the alkali metal salt thereof and can include a mixture of two or more stabilisers.
The activator is preferably selected from the group which releases peroxyaceticacid on reaction with hydrogen peroxide. Exemplifying of this group are tetraacetylethylenediamine (TAED), pentaacetylglucose (PAG), N- acetylcaprolactam. More generally, sodium nonanoyloxybenzenesulphonate, (producing peroxynonanoic acid on reaction with hydrogen peroxide) ethylidenebenzoateacetate and ethylideneheptanoate acetate can be used or mixtures thereof. The activator is advantageously present at a level of from 5- 10% w/w and particularly advantageously at 7-9% w/w.
The second solution can include a corrosion inhibitor such as benzotriazole or other inhibitors known in that art. The corrosion inhibitors find particular use where the disinfection use is to include application to a metal surface, and will be present at a level of from 0.4% to 0.8% by weight of the second solution.
Advantageously, the first solution includes an organic diol. The diol enables
higher concentration solutions of borates to be achieved. The diol is particularly advantageously a cis - 1, 2 - diol, or a -1, 3- diol which can bond more readily with borate. Suitable diols for consideration are sorbitol, mannitol, xylitol, gluconic acid or salt thereof, dextrins, maltoses etc. The diol is conveniently present at a level of from 0.5% to 2% w/w.
The ratio of first solution to second solution is preferably between 1 :3 and 3: 1 by volume, and particularly preferably 1 : 1.
The invention also includes a two pack system for use in disinfecting surfaces, the system including a first pack comprising hydrogen peroxide at a concentration of up to 8% w/w, an alkali metal borate salt, and a peroxide stabiliser, the second pack comprising an activator reactable with hydrogen peroxide to form a peroxyacid; a structuring electrolyte, the second pack having a pH of from 6 to 10.
A disinfectant composition comprising a non-equilibrium solution of peroxyacid and hydrogen peroxide, the composition having a pH of from 7 to 10, and including a borate salt, and a peroxide stabiliser.
Brief Description of the Drawing
The invention will now be described with reference to the accompanying drawing. In the drawing:
Figure 1 is a line plot of peroxyacetic acid generation for the systems of Table 1.
Detailed Description of the Invention
In order to provide in-situ generation of a peroxyacid, a number of problems need to be addressed. Amongst these problems are the need to prevent the components which form the peroxyacid from reacting before they are required to. There is also a need to generate the peroxyacid at the required rate: too slow a rate can result in a lack of performance and too high a rate in wastage of peracid through inefficient side reactions and also possibly result in an unsafe composition.
One solution to the first problem is to provide a system in which the reaction
elements are maintained separately until required. Such a solution to the problem is contemplated in the invention described herein.
In order to generate a peroxyacid, the most commonly used source of the peroxide moiety is hydrogen peroxide itself. The peroxyacid is generated through the reaction of hydrogen peroxide via a nucleophilic pathway, with an acyl containing molecule. Carboxylic acids themselves are not normally sufficiently reactive and so an activated form of acyl group is often used. Compounds which include such an activated acyl group are normally referred to as activators.
Furthermore, although the peroxide anion, HO2 ", is a relatively strong nucleophile, hydrogen peroxide itself is not. Reaction can therefore often be slow, particularly when the pH of the solution is a number of units away from the pKa value of hydrogen peroxide, which is approximately 11.
In the following, peroxyacid generation is described predominantly in relation to peroxyacetic acid. It will be appreciated that the method is applicable to other peroxyacids.
As demonstrated below, the presence of a soluble borate increases the rate at which peroxyacid is generated. Whilst not wishing to be bound by theory, it is believed that hydrogen peroxide and borate anions react together to form an anionic peroxoborate species in solution. Peroxoborate anions are better nucleophiles than hydrogen peroxide itself, and so react more readily with the activator, to generate peroxyacid at pHs of 7 to 9.5, and especially so in the more acidic solutions.
This effect is demonstrated in the following experiments which show the effect of the presence of an activating species such as borate anion as shown below. The results were obtained as follows: to a suspension of Tetraacetylethylenediamine (TAED) in deionised water, hydrogen peroxide was added rapidly with good mixing. The hydrogen peroxide and peroxyacetic acid levels were then monitored at time intervals. In Table 1, a comparison is shown for a system in which disodium tetraborate (DTB) was included, pre-mixed with the hydrogen peroxide.
The hydrogen peroxide was determined by titration against cerium (IV) sulphate. The peroxyacetic acid level was determined by first titrating against cerium (IV) sulphate to remove hydrogen peroxide and subsequently titrating against sodium thiosulphate in the presence of potassium iodide. The results obtained are shown in Table 1 as follows:
Table 1
The pH of each system was monitored during the experiment, and the results are shown in Table 2:
Table 2
The results in Table 1 are plotted on the graph shown in Figure 1. As can be seen, the addition of disodium tetraborate increases the rate of peroxyacetic acid production for a solution having 7.5 % w/w hydrogen peroxide, to a level comparable with that obtained when 18% w/w hydrogen peroxide is present.
Further experiments, (4) and (5), were run in which N-Acetylcaprolactam was
used as the activator. In order to provide the equivalent number of labile acetyl groups to generate the peroxyacetic acid, the molar concentration of N- acetylcaprolactam was twice that of the TAED in Experiments (1) - (3) above. The results are given in Table 3 below:
Table 3
The pH of each system was monitored during the experiment and the results are shown in Table 4:
Table 4
The results from Table 3, together with the results from column (3) of Table 1 are plotted in Figure 1. As can be seen from Figure 1, the presence of DTB results in a greater rate of generation of peroxyacetic acid.
In line with the above, a two component system containing TAED as activator and exemplifying the invention is as given below. The system has two aqueous compositions A and B which are constituted as follows:
Composition A
69.85% w/w Deionised Water 7.1% w/w p-dodecylbenzensulphonic acid 0.60% w/w Benzotriazole
0.85% w/w Sodium Hydroxide
0.01% 7W Diethylenetriamine(pentamethylenephosphonicacid)
4.0 % w/w Isodecylalcohol ethoxylate
10.1% 7
W Trisodium Citrate 0.004% FD & C Green Dye
Composition A is a structured liquid having a pH of around 7.
Composition B
3.10% 7W Disodium Tetraborate 88.80% w/wDeionised Water
0.50% w/w Diethylenetriamine(pentamethylenephosphonicacid) 7.00% 7W Hydrogen Peroxide
0.60% 7W Sodium Hydroxide
When devising a system to generate a peroxyacid it is important that the constituent parts of the compositions do not separate out, so that the chemical make up of the composition remains consistent throughout the composition during storage. This is particularly relevant for the composition containing the borate, as the aqueous solubility of the borate - for example, disodium tetraborate - is not particularly high, with the result that insoluble material can easily be present if the overall concentration of borate in the composition became too high. As the borate salts are relatively dense they would not easily form into a stable suspension, and so the solid borate would settle out.
The user therefore has two obvious problems in using a two pack system as herein contemplated. Firstly, the user will not be certain of delivering the correct amount
of borate or peroxoborate species into the mixed composition, as a significant proportion of the borate species will have settled to the bottom of the pack. The amount and rate of generation of peroxyacetic acid will therefore be inconsistent between batches. Secondly, even if agitation of the borate-containing composition is undertaken prior to its being mixed with the other composition, the production of peroxyacetic acid is slowed down. The slowing is due to the introduction of a dissolution step in which the borate dissolves, prior to conversion of borate to peroxoborate. The time required to reach a required concentration of peroxyacetic acid will therefore be longer.
In order to overcome this problem therefore, it has been found advantageous to include a dissolution aid, often in the form of a diol. The diol undergoes a dehydration reaction with the hydroxy groups of the borate. The resultant species is more soluble than the original borate, effectively rendering a higher concentration borate solution, but does not, surprisingly, decrease the reactivity with hydrogen peroxide to form peroxoborate solutions. Such an increased concentration of borate species therefore increases the equilibrium concentration of peroxoborate species in solution. As a result, on mixing the borate-containing composition with the composition containing the activator, peroxyacetic acid generation is more rapid. Moreover, less of the two compositions is required to achieve a given peroxyacetic acid concentration inside a given time-scale.
The effect of a number of diols on the solubility of disodium tetraborate is shown in the following table:
Table 5: Solubility of Disodium Tetraborate in a Solution.
Table 5 shows the number of moles of disodium tetraborate which can be
dissolved in a Standard volume of the particular solution before the solution becomes saturated. As can be seen from the results, a higher concentration of tetraborate can be achieved in the presence of a molecule having a diol group.
Similar remarks concerning settling of solid components may also be applied to the solution containing the activator where the activator is present as a solid. It is important therefore that the activator be prevented or hindered from settling out. To this end a structuring agent, such as citric acid or a salt thereof is included in the solution. Without being bound by theory it is believed that the structuring agent causes ordering of the water and other constituents of the solution into a structure capable of supporting the solid components. A suitable concentration for the structuring agent is from 7-12% w/wand preferably 9-11% w/w.
The following example gives an illustration of a composition suitable for use:
Example 1
A first composition C was prepared by mixing together the following:
Tetraacetylethylenediamine (TAED) 8.50% w/w. Dodecylbenzenesulphonic acid 6.95% w/w.
C10 - Fattyalcohol Ethoxylate 3.98% w/w.
Sodium Hydroxide (47% w/w) 1.92% w/w.
Trisodium Citrate (40% w/w) 24.82% w/w.
Benzotriazole 0.60% w/w. Deionised Water 53.23% w/w.
The overall composition formed was a white suspension having a pH of approximately 8. As examples of commercially available anionic surfactants, para - dodecylbenzenesulphonic acid, with minor amounts of Cio - CB secondary alkylbenzenesulphonic acids, can be cited. A suitable fattyalcohol ethoxylate is one derived from an isodecylalcohol with minor amounts of Ci2 - C15 alcohols.
A second composition D was prepared by mixing together the following:
Hydrogen Peroxide (35% w/w) 21.53% w/w.
Diethylenetriamine(pentamethylenephosphonicacid) 0.33% w/w.
Disodium Tetraborate 4.06% w/w.
Sorbitol 1.27% w/w. Sodium Hydroxide (47% w/w) 2.00% w/w.
Deionised Water 70.81% w/w.
The diethylenetriaminepenta(methylenephosphonic acid) is normally supplied as its sodium salt solution (32% as sodium salt). The second composition was a clear solution having a pH of approximately 9.
The preparation of the second composition itself took place in three stages. Firstly, a solution of the sorbitol was prepared containing the following:
Sorbitol 1.82% w/w.
Disodium Tetraborate 5.80% w/w.
Diethylenetriamine(pentamethylenephosphonicacid) 0.60% w/w. Deionised Water 91.78% w/w.
A sodium hydroxide solution was also prepared containing the following:
Sodium Hydroxide (pearl) 47.00% w/w.
Diethylenetriamine(pentamethylenephosphonicacid) 0.60% w/w.
Deionised Water 52.40% w/w.
The sorbitol solution and the sodium hydroxide solution were then mixed with the other constituents shown for composition D in the following amounts to form composition D.
Sorbitol Solution 70.00% w/w.
Diethylenetriamine(pentamethylenephosphonicacid)
0.60% w/w.
Hydrogen Peroxide (35% w/w) 22.10% w/w.
Sodium Hydroxide solution 2.00% w/w. Deionised Water to 100% w/w.
On mixing composition C (17ml) with composition D (17ml) in 1 litre of water, a solution containing approximately 0.1%w/w peroxyacetic acid was generated after 10 minutes.
In the above composition, benzotriazole has been included as a corrosion inhibitor. Such corrosion inhibitors would normally be used in, for example, instrument sterilisation in hospitals, where they reduce pitting of metal instruments. For other uses, such as animal health, the corrosion inhibitor can be dispensed with and so not included in the compositions.
In addition to or in place of benzotriazole, other corrosion inhibitors may also be present. For example, the benzotriazole may contain one or more substituents on either the benzene ring or on one or more of the nitrogens of the triazole group. As examples of such substituents are lower alkyl groups having up to six carbon atoms, carboxy groups, hydroxy groups, or combinations thereof. Further examples of corrosion inhibitors include alkali metal borates, phosphates or polyphosphates, sodium molybdate, benzoic acid or salts thereof.
As indicated above, the activator is included as a source of peracid precursor. A number of other activators known in the art, can also be used therefore either alone or in combination with TAED or other such activators. For example, oxybenzenesulphonic acid, such as nonanoyloxybenzenesulphonic acid, or the salts thereof can be used. Also to be considered are N-acylcaprolactams or N- acylvalerolactams such as N-acetylcaprolactam. Further well known examples of peracid precursors suitable for use are pentaacetylglucose or N,N,N,N- tetraacetylglycoluril (TAGU).
Similarly, the diol can be chosen to achieve the desired concentration of borate in solution. Amongst the diols, -1,2-diols are particularly suitable as they are stereochemically in the correct configuration to form a borate ester. However, - 1,3- ; -1,4 - and other diols can also be used. Moreover, polyhydroxy molecules can also function in the same manner as diols themselves, through the use of two of their hydroxy groups to engage with the borate molecule.
Exemplary of diol-containing molecules are fructose, galactose, glucose, mannose, ribose, erythrose, lactose, sucrose, saccharose, sorbitol, xylitol, xylulose, glycerol, glycerol monoalkyl ether, gluconic acid, galactonic acid, mannonic acid, glucuronic acid, dextrins, maltoses or a cellobiose.
In addition to or in combination with
Diethylenetriamineφentamethylenephosphonicacid), other chelating agents, to stabilise peroxide, can be included in the compositions. As examples, only, of such chelating agents are other alkylideneaminophosphonic acids or salts thereof, some of which are marketed under the name Dequest . Exemplary thereof are 1- hydroxyethylidene-1 , 1 -diphosphonic acid, 1 -amino- 1 -cyclohexylmethane- 1,1- diphosphonic acid, 1 -amino- 1-phenylmethanediphosphonic acid, amino (trimethylenephosphonic acid), dimethylaminomethanediphosphonic acid, and 1- hexamethylenediaminetetra(methylenephosphonic) acid. A further class of compounds suitable for use are the aminocarboxylicacids or salts thereof. As examples, only, of members of this class are ethylenediaminetetraacetric acid, nitrilotriacetic acid, ethylenediaminedisuccinic acid, diethylenetriaminopentaa- cetic acid, N-di(methylenephosphonic acid)-aminoacetic acid.
In addition, also, suitable as chelating agents are dipicolinic acid, ethane-1, 1,2- triphosphonic acid, ethylidene- 1,1 -diphosphonic acid, phosphono-succinic acid, 1- phosphono-lmethylsuccinic acid. Furthermore, also well known in the art as chelating agents are phosphates, polyphosphates and pyrophosphates of monovalent cations, primarily sodium. Also polymeric carboxylates such as polyacrylic acid or salts thereof can also function as chelating agents. The stabiliser or stabilisers should be present in sufficient amounts to inhibit breakdown of hydrogen peroxide to allow the solutions to be stored. Levels of stabiliser of 0.3-0.6% w/w have been found to be suitable for this purpose.
In addition to or in combination with the anionic surfactant p- dodecylbenzensulphonic acid exemplified, other anionic surfactants can be included in the compositions. Amongst these are alkyl-, aryl-, alkylaryl- or arylalkyl-, sulphates or sulphonates having from 6 to 22 carbon atoms, usually present as their alkali metal salt, such as sodium laurylsulphonate or sodium laurylsulphate. Also suitable are ether sulphates or sulphonates containing alkyl-,
aryl-, alkylaryl- or arylalkyl- sulphonic acids or alkali metal salts thereof. As commercially available examples of such anionic surfactants are linear alkylbenzenesulphonates under the name NANSA™ from Albright and Wilson, or HOSTAPUR™ from Hoechst. Other suitable anionic surfactants are for example naphthalenesulphonic acid, alkylnaphthalene sulphonic acids, or alkali metal salts thereof.
A further group of anionic surfactants which are suitable for use are alkylether sulphates. One subgroup thereof is the alkyl(ethylether)sulphates characterised by the general formula R2-O-(Cm H2mO)n - SO3M in which:
R2 is an alkyl group, preferably having 12-18 carbon atoms; m = 2 n = l-10
M is an alkali metal, ammonium, substituted ammonium ion, but is preferably sodium.
As further examples of anionic surfactants the class derived from sarcosine can be named.
Whilst borate is the anion of choice, other inorganic anions which are suitable are phosphates and sulphates.
It will of course be understood that the invention is not limited to the specific details described herein, which are given by way of example only, and that various modifications and alterations are possible with the scope of the appended claims.