GB2288979A - Sterilising compositions - Google Patents

Abstract

A bleach activator of the type commonly used in laundry detergents is used to activate a peroxygen bleach used to sterilise a prosthesis removed from the body before reinsertion. The prosthesis may be a set of dentures, contact lens or a diaphragm. The bleaching solution is subsequently neutralised with a neutraliser compound which reacts with peroxygen bleaching species. The neutraliser may be an a -ketoacid, preferably pyruvic acid. The compositions may contain an indicator which changes colour upon neutralisation of old bleaching species. The pH of the sterilising solution is preferably in the range 4 up to the pKa of the protonated form of the bleaching species, which is usually a percarboxylic acid. Preferably the pH is in the range 4-7.7. Activation of the peroxygen bleach source allows improved sterilisation to be achieved, whilst neutralisation gives improved comfort to the wearer and is particularly desirable for removal of percarboxylic acid species present in the sterilising solution.

Description

CLEANSING COXPOS ITIONS The present invention relates to compositions for cleansing a substrate, for instance dentures and/or contact lenses, by using an aqueous solution containing a peroxygen bleach source and a bleach activator for a period sufficient to allow cleansing to take place, followed by contacting the substrate with a neutraliser which neutralises any peroxygen bleach species present.

It is known to use hydrogen peroxide solutions as disinfection means for various medical applications, as well as for treating hydrophilic contact lenses. Where the solutions are used with hydrophilic contact lenses, it is generally necessary to contact the treated lenses with a neutraliser for the hydrogen peroxide prior to the lenses being reintroduced into the eye. In EP-A-0,110,609 there is disclosed a cleansing regimen in which lenses sterilised by immersion in hydrogen peroxide solution are subsequently treated with a solution of sodium pyruvate.

Pyruvate neutralises hydrogen peroxide in a reaction in which the pyruvate is decarboxylated to form acetate and carbon dioxide. Other organic compounds which react in a similar way with hydrogen peroxide are a-ketocarboxylic acids such as a-ketoglutarate, a-ketobutyrate and a-ketoadipate. Other organic compounds which have been suggested as neutralisers for hydrogen peroxide include salts of fumaric acid, maleic acid, lactic acid and citric acid.

It has also been suggested to neutralise hydrogen peroxide by adding an enzyme which catalyses the breakdown of hydrogen peroxide into water and oxygen. Enzymes which catalyse this reaction are catalase and peroxidase. In EP-A-0,367,723 the use of catalase to decompose hydrogen peroxide is disclosed. That reference also suggests the use of non-enzymic catalysts for hydrogen peroxide breakdown, for instance platinum.

In EP-A-0,054,358 hydrogen peroxide is decomposed by reaction with aniline or an aniline derivative in the presence of a peroxidase enzyme. The reaction is used either for decomposing hydrogen peroxide remaining in a food for which it has been used as bleaching agent, or for use in an assay for determining the presence of an enzyme which catalyses the production of hydrogen peroxide from a particular substrate.

Enzymic reactions in which hydrogen peroxide is produced by the reaction are often identified by analysing for hydrogen peroxide produced using various chromogenic reaction systems. Many of these are based on the NAD/NADH or NADP/NADPH and a dye compound capable of accepting electrons from the product. EP-A-0,317,070 describes a colorimetric assay for various biologically important enzymes.

In EP-A-0,400,858, GB-A-2,213,159, EP-A-0,323,049, US-A-5,055,305 and EP-A-0,400,858, denture cleansing tablets containing a peroxygen source, an activator and a compound capable of making the composition effervescent are described for cleansing dentures. The tablets generally comprise two components eg provided in separate layers, a rapidly dissolving acidic component which contains the activator and a more slowly dissolving alkali component which contains the peroxygen source. The acidic component may contain tartaric and/or citric acid. The compositions may also include enzymes, apparently to provide improved cleansing performance by catalysing breakdown of components adherent to the dentures. The compositions may also contain a chelating agent which is said to stabilise the bleaching species formed.

In EP-A-0,334,060 and US 5,015,408 denture cleaning tablets are disclosed which may contain a peroxygen bleach source, a bleach activator and a chelating agent which is a phosphonic acid derivative. It is disclosed that the compositions may also contain a colour indicator which indicates the end of the reaction. The indicator is a combination of two dyes, one of which is a redox dye having a relatively weak redox potential, and the other of which is independent of the redox potential. One example of a suitable combination is indigo L-blue 2 and quinoline Lyellow 3.

In EP-A-0,400,858 an indication system is included which contains FDC Blue 02 and sulphuric acid which turns from coloured to colourless when cleansing is complete.

The indicator system is present in the solution throughout the cleansing period.

In a new process according to the invention for treating a substrate the following steps are carried out: a) formation of an aqueous solution containing peroxygen bleach source and a bleach activator which react to form a peroxygen bleaching species, b) contacting the aqueous solution formed in a) with the substrate for a period of time sufficient to sterilise the substrate, c) contacting the substrate after step b) with a neutralising compound which reacts with any excess peroxygen bleach source and peroxygen bleach species present.

The process of the invention is of particular value for treating prostheses which are removed from the body and subsequently inserted back into a body cavity. For instance the prosthesis may be a set of dentures, a contact lens or a diaphragm. Alternative uses for the process include the bleaching/disinfection of food products and the disinfection of hard surfaces, for instance medical implements.

In the process it is generally unnecessary for the substrate to be rinsed between steps b) and c), although in some instances it may be convenient to include a rinse step. A suitable rinsing medium is water or another aqueous solution, for instance a buffered solution, usually a saline solution, for instance an isotonic buffered saline solution.

The neutralising step, step c), may be carried out by introducing into the solution of step a) a composition containing the neutralising compound. Preferably, however, the solution from step a) is discarded before contacting the substrate with a separate solution containing the neutralising compound. In an alternative process, the neutralising compound is present in the reaction medium for step b), but in an inactivated form, and step c) commences upon activation of the neutraliser. Inactivation may, for instance, be by keeping the neutralising compound out of solution, for instance by encapsulating it or otherwise formulating it so that it is not released into solution until step b) has continued for a sufficient length of time.

In the process the peroxygen bleach source may be hydrogen peroxide or an organic or inorganic percompound.

Preferably the peroxygen source is an inorganic persalt, for instance a perborate, percarbonate, persulphate or other percompound. The appropriate source is selected for optimal compatibility with other components, desired pH and non-toxicity.

The activator compound is preferably an acyl donor, usually an N-acyl or O-acyl donor. Preferably the activator is a compound of the formula I

in which L is a leaving group and R is an alkyl, aralkyl, alkaryl, or aryl group, any of which groups has up to 24 carbon atoms and may be substituted or unsubstituted.

The leaving group L is preferably a compound the conjugate acid of which has a pKa in the range 4 to 13, preferably 7 to 11, most preferably 8 to 11.

It is preferred that R1 is an aliphatic group preferably a C118 alkyl group, or an aryl group.

In the present invention the term alkyl includes alkenyl and alkyl groups may be straight, branched or cyclic.

In the formula I L and R1 may be joined to form a cyclic compound, usually a lactone or a lactam. These cyclic groups may include heteroatoms, for instance oxygen or optionally substituted nitrogen atoms, carboxyl groups as well as -CH2- groups or substituted derivatives thereof.

They may be saturated or unsaturated. L can itself comprise a cyclic group, including heterocyclic groups, for instance joined to the C=O group of the compound I via the heteroatom.

Substituents on R1 and L can include hydroxyl, =N-R2 in which R2 is selected from any of the groups represented by R1 and is preferably lower alkyl, amine, acyl, acyloxy, alkoxy, aryl, aroyl, aryloxy, aroyloxy, halogen, amido, and imido groups and the like as well as other groups not adversely affecting the activity of the compound.

In the invention the compound of the formula I can be any acyl-donor compound, usually an N-acyl or O-acyl compound, which has been described as a bleach activator for use in laundry detergents. The compound of the formula I may be an anhydride, but is preferably an ester or, even more preferably, an amide derivative.

Amide derivatives include acyl imidazolides and N,N-di acylamides. Other examples of N-acyl derivatives are: a) 1, 5-diacetyl-2 , 4-dioxohexahydro-1, 3, 5-triazine (DADHT); b) N-alkyl-N-suphonyl carbonamides, for example the compounds N-methyl-N-mesyl acetamide, N-methyl-N-mesyl benzamide, N-methyl-N-mesyl-p-nitrobenzamide, and N-methyl- N-mesyl-p-methoxybenzamide; c) N-acylated cyclic hydrazides, acylated triazoles or urazoles, for example monoacetyl maleic acid hydrazide; d) O,N,N-trisubstituted hydroxylamines, such as O-benzoyl N,N-succinyl hydroxylamine, O-p-nitrobenzoyl-N,N-succinyl hydroxylamine and O,N,N-triacetyl hydroxylamine; e) N,N'-diacyl sulphurylamides, for example N,N'-dimethyl N,N'-dimethyl-N,N'-diacetyl sulphuryl amide and N,N'diethyl-N,N'-dipropionyl sulphurylamide; f) 1, 3-diacyl-4, 5-diacyloxy-imidazolines, for example 1,3diformyl-4,5-diacetoxy imidazoline, 1,3-diacetyl-4,5diacetoxy imidazoline, 1,3-diacetyl-4,5-dipropionyloxy imidazoline; g) Acylated glycolurils, such as tetraacetyl glycoluril and tetraproprionyl glycoluril; h) Diacylated 2,5-diketopiperazines, such as 1,4-diacetyl 2, 5-diketopiperazine, 1, 4-dipropionyl-2, 5-diketopiperazine and 1,4-dipropionyl-3,6-dimethyl-2,5-diketopiperazine; i) Acylation products of propylene diurea and 2,2-dimethyl propylene diurea, especially the tetraacetyl or tetrapropionyl propylene diurea and their dimethyl derivatives; j) Alpha-acyloxy-(N,N')polyacyl malonamides, such as alpha-acetoxy-(N,N')-diacetyl malonamide.

k) O,N,N-trisubstituted alkanolamines, such as O,N,Ntriacetyl ethanolamine.

Alternatively the compound may be an ester, for instance 1) N-acyl lactams, such as N-benzoyl-caprolactam, N-acetyl caprolactam, the analogous compounds formed from C410 lactams.

m) N-acyl and N-alkyl derivatives of substituted or unsubstituted succinimide, phthalimide and of imides of other dibasic carboxylic acids, having 5 or more carbon atoms in the imide ring.

Alternatively the compound may be an ester, for instance n) sugar esters, such as pentaacetylglucose, o) esters of imidic acids such as ethyl benzimidate, p) triacylcyanurates, such as triacetylcyanurate and tribenzoylcyanurate, q) esters giving relatively surface active oxidising products for instance of C818-alkanoic or -aralkanoic acids such as described in GB-A-864798, GB-A-1147871 and the esters described in EP-A-98129 and EP-A-106634, for instance compounds of the formula I where L comprises an aryl group having a sulphonic acid group (optionally salified) substituted in the ring to confer water solubility on a benzyl group, especially nonanoyloxybenzenesulphonate sodium salt (NOBS), isononanoyloxybenzenesulphonate sodium salt (ISONOBS) and benzoyloxybenzenesulphonate sodium salt (BOBS) r) phenyl esters of C14.22-alkanoic or -alkenoic acids, s) esters of hydroxylamine, t) geminal diesters of lower alkanoic acids and gem-diols, such as those described in EP-A-0125781 especially 1,1,5triacetoxypent-4-ene and 1,1,5, 5-tetraacetoxypentane and the corresponding butene and butane compounds, ethylidene benzoate acetate and bis(ethylidene acetate) adipate and u) enol esters, for instance as described in EP-A-0140648 and EP-A-0092932.

Where the activator is an anhydride it is preferably a solid material, and is preferably an intra-molecular anhydride, or a polyacid polyanhydride. Such anhydride compounds are more storage stable than liquid anhydrides, such as acetic anhydride. Anhydride derivatives which may be used as activator include v) intramolecular anhydrides of dibasic carboxylic acids, for instance succinic, maleic, adipic, phthalic or 5norbornene-2,3-dicarboxylic anhydride, w) intermolecular anhydrides, including mixed anhydrides, of mono- poly-basic carboxylic acids, such as diacetic anhydride of isophthalic or perphthalic acid x) isatoic anhydride or related compounds such as described in WO-A-8907640 having the generic formula II

wherein Q is a divalent organic group such that Q and N together with the carbonyl groups and oxygen atom of the anhydride group form one or more cyclic structures and R2 is H, alkyl, aryl, halogen or a carbonyl group of a carboxyl containing function; or benzoxazin-4-ones as described in WO-A-8907639, that is compounds of the formula III

wherein Q' is selected from the same groups as Q and R3is H, alkyl, aryl, alkaryl, aralkyl, alkoxyl, haloalkyl, amino, aminoalkyl, carboxylic group or a carbonylcontaining function; preferably 2-methyl-(4H)3,1benzoxazin-4-one (2MB4) or 2-phenyl-(4H)3,1-benzoxazin-4one (2PB4); y) polymeric anhydrides such as poly(adipic) anhydride or other compounds described in our co-pending application WO A-9306203.

In the process the neutralising compound is preferably a compound which reacts with hydrogen peroxide. The compound is usually a carboxylic acid compound, especially a a-keto acid, which reacts by a decarboxylation reaction.

Suitable a-keto acids are a-ketoglutaric, a-keto-butyric, a-ketoadipic (or a,a'-diketoadipic) and, preferably, pyruvic. Suitable neutralising compounds are in the form of salts, usually alkali metal salts.

Alternatively the neutraliser compound may comprise an enzyme, for instance selected from peroxidase and catalase, or may comprise a non enzymic catalyst for peroxygen decomposition, such as platinum, or other catalytic metals or metal salts.

After the neutralisation step, where the substrate is a prosthesis, it may be ready for direct insertion into a body cavity, or may be subjected to a rinse step before reinsertion. It is preferred for the solution in the neutralising step to comprise isotonic saline solution, for instance a buffered saline solution, provided this is compatible with the neutralising step.

In the process it is particularly convenient for an indicator to be included in the neutralising step which will provide an indication, preferably a visual indication, as to when the neutralising step is complete, that is when substantially all the peroxygen bleach source and peroxygen bleaching species has been neutralised. Suitable indicator components for use include the dye system disclosed in EP 0,400,858 and EP-A-0,334,060 (and US 5,015,408). Such an indicator system may be present in the neutralising mixture at the start of neutralising step c), or may be added after a predetermined period of neutralisation. The indicator system may comprise dissolved components or the components may be immobilised, for instance on a surface of the vessel in which the neutralising step is being carried out. Where the components of the indicator system are immobilised, the indicator reaction is reversible, so that the vessel can be re-used again and again.

The reagent mixture for step b) preferably comprises a sequestrant, which is capable of inhibiting the disadvantageous interaction of heavy metals on the perhydrolysis step in which the peroxygen source and the activator react and/or on the subsequent activity of bleaching species formed. Suitable sequesterants are, for instance, amino carboxylic acids and, preferably, poly(methylene phosphonic acids).

The present invention provides also compositions and combinations of compositions suitable for carrying out the process. Usually the bleach source and the activator are included in the same composition. It is preferable for them to be kept separate from one another within the composition in order to improve the storage stability of the composition. This may be achieved using compounding methods known from the laundry detergent field, where peroxygen sources and activator compounds are frequently incorporated into solid compositions. Where the composition is granular in form, the peroxygen source and activator may be components of the same granule, but are preferably included in the composition in separate granules. The granules may be formed by conventional techniques such as by spray drying, by melt granulation/ extrusion techniques using a meltable binder or by granulation by spraying a granulating liquid onto a moving bed of activator or peroxygen source (as the case may be) particles including a particulate polymeric binder, for instance as described in EP-A-0,037,026 and EP-A-0,238,341.

In another technique for forming particulate solids containing either peroxygen source or activator, the active ingredient may be microencapsulated, by the provision of a polymeric wall surrounding the active ingredient whilst suspended in a continuous non-solvent phase.

Microencapsulation techniques are of particular value where it is desired to provide one of the components in a delayed release form. The material forming the wall can be selected so as to allow for dissolution and release after a predetermined period of time.

Suitable microencapsulation techniques, which may also be termed coacervation techniques, generally consist of a process in which the bleach component is dispersed to form discrete islands of dispersed phase in a liquid continuous phase and a polymeric coating is formed at the interface between the dispersed phase and the continuous phase, followed by recovery of the coated particles. There may be an optional drying step in which the continuous phase is removed as well as a drying step in which any solvent in the dispersed phase is removed. Coacervation techniques suitable for the wall formation step are described in, for instance, GB-A-1,275,712, GB-A-1,475,229, GB-A-1,507,739 and DE-A-3545803. Usually two counterionic polymers are used to form the wall.

Coacervation techniques may be particularly suitable for formulating the neutralising compound for incorporation into a composition which contains also ingredients for carrying out the sterilisation step b). The polymer forming the wall can be selected so that the neutralising compound is not released until the peroxygen source and activator have had sufficient time to react to form bleaching species for sterilising the substrate.

The components of the composition may be provided in granular form, for instance in a package comprising a single unit dosage. Convenient forms include sachets to be torn by the user for dispensing into water. Alternatively the composition may be provided in tablet form, in which particulate ingredients are pressed together to form a tablet. The tablet may comprise several layers to allow sequential dissolution of components. For instance the outer layer may comprise the activator, the next layer may comprise the peroxygen source and the inner layer may comprise the neutraliser. The tablet or layers within the tablet may be coated eg with delayed release coating. A tablet or some layers of a tablet may comprise ingredients which increase disintegration and/or dissolution. For instance the compositions may comprise salts which make the tablet effervescent, for instance as described in EP-A-0,400,858 etc. mentioned above. Disintegration aids may include swellable compounds such as swellable cellulose derivatives well known in the tabletting field.

Where the process provides for means to indicate the end of the neutralisation step, the indicator means may be incorporated into a complete composition which contains all the other ingredients or, alternatively, may be incorporated into either the composition or the layer of a tablet containing the bleach compounds or the composition or layer of tablet containing the neutralising compound where those are separate. Alternatively the indicator may be immobilised upon a solid support, for instance the wall of the reaction vessel.

The compositions of the invention may include other usual components of cleansing tablet formulations, especially surfactants chelating agents, enzymes, pigments/dyes, flavour oils such as oils of spearmint, peppermint and winter green, dyestuffs, sweeteners, foam depressants such as dimethyl polysiloxanes, foam stabilisers such as the fatty acid sugar esters, preservatives, lubricants such as talc, magnesium stearate, finally divided amorphous pyrogenic silicas etc.

A surface activation used in the compositions of the invention can be selected from the many available which are compatible with other ingredients of the cleanser composition, for instance ingredients commonly used in denture cleansers. Such materials are believed to improve the effectiveness of the other ingredients by aiding their penetration into the inter dental surfaces and aiding in removal of food debris. Preferably the amount of surface active agent is up to 5% by weight of a dry composition.

In the addition to the heavy metal sequesterants mentioned above which aid in stabilisation of the bleach species formed in the process, it may be desirable to include chelating agents which aid removal of calcium from dentures. Examples of suitable chelating agents for this function include sodium tripolyphosphate, sodium pyrophosphate, tetrasodium pyrophosphate, imino polycarboxylates such as nitrilotriacetic acid and ethylene diamene tetraacetic acid and salts thereof.

Another component suitable for inclusion in compositions of the invention are cobiocides and proteolytic enzymes.

In the process, the aqueous solution formed in step a) and used to sterilise the substrate preferably has a pH which is in the range pH 4 up to pK, of the protonated form of the peroxygen bleaching species, or that pK. less 0.5 unit. Where the bleach activator is an acyl donor, then it is the pK, of the corresponding carboxylic acid which determines the preferred pH. For instance where the activator is acetyl derivative, the bleaching species is presumed to be peracetic acid. The pK, of peracetic acid is 8.2. Accordingly the pH of the solution used in step b), where the activator is an acetyl derivative is preferably 4-8.2, preferably up to 7.7. Preferably the maximum pH is 1 unit less than the pX of the respective acid, more preferably 1.5 units less.

To achieve the desired pH it is desirable to incorporate acidifiers or buffers into the composition used in the invention. For instance the acidifying component may comprise a polybasic organic acid, such as a polybasic carboxylic acid such as citric, succinic, or adipic acid or sulphamic acid. Alternatively the component may react with a by-product of the reaction of the peroxygen source and activator to make an acid. Where perborate is used as peroxygen source, borate is a by-product and so any component known to react with borate to drop the pH, eg cis-1,2-diols, such as glycols and polyols, boric acid, or sodium dihydrogen phosphate can be used. Such acidifying components are also suitable for use where percarbonate is the peroxygen source.

The following example illustrates the invention.

Example 1 The following components were dissolved into 1 e of water: sodium perborate tetrahydrate 17.5 g citric acid 8 g TAED 2.6 g sodium bicarbonate 0.5 g EDTA 0.25 g surfactant 0.2 g.

Upon dissolution of the components into water, the compositions were used to cleanse sets of dentures. After a predetermined period of time, for instance in the range 5 minutes to 12 hours, usually at least 10 minutes, the solution is poured off and a new solution containing sodium pyruvate at a concentration in the range 0.5 to 5% by weight, for instance around 1% by weight, was contacted with the drained dentures. The solution was left in contact with the dentures for a period of at least 1 minute, preferably in the range 5 to 30 minutes, after which the oxidising species, residual peroxide, had been removed by neutralisation.

Example 2 Example 1 was repeated but using a combination of polymethylene phosphonic acid salts with the amino carboxylic acid sequestrant. The solution acted as a cleansing agent for dentures and the pyruvate neutralisation step resulted in complete removal of residual bleaching species.

Example 3 Example 1 was repeated but using in place of the citric acid, sodium dihydrogen phosphate, in an amount of 17.5 g.

Claims (25)

1. A process for treating a substrate comprising the following steps: a) formation of an aqueous solution containing peroxygen bleach source and a bleach activator which react to form a peroxygen bleaching species, b) contacting the aqueous solution formed in a) with the substrate for a period of time sufficient to sterilise the substrate, c) contacting the substrate after step b) with a neutralising compound which reacts with any excess peroxygen bleach source and peroxygen bleach species present.

2. A process according to claim 1 in which the substrate is a prosthesis which has been removed from the body for the treatment.

3. A process according to claim 2 in which the substrate is a set of dentures, a contact lens or a diaphragm.

4. A process according to any preceding claim which includes a rinsing step between steps b) and c).

5. A process according to claim 4 in which the substrate is rinsed with isotonic saline solution.

6. A process according to any preceding claim in which the activator is an N-acyl or O-acyl donor.

7. A process according to claim 6 in which the activator is a compound of the formula I

in which L is a leaving group and R is an alkyl, aralkyl, alkaryl, or aryl group, any of which groups has up to 24 carbon atoms and may be substituted or unsubstituted.

8. A process according to claim 7 in which the leaving group L is preferably a compound the conjugate acid of which has a PKa in the range 4 to 13, preferably 7 to 11, most preferably 8 to 11.

9. A process according to claim 7 or 8 in which R1 is a C1.18-alkyl group.

10. A process according to any of claims 7 to 9 in which the activator is an N-acyl derivative.

11. A process according to claim 10 in which the activator is an N,N-diacylamide, preferably tetraacetylethylene diamine.

12. A process according to any preceding claim in which the neutralising compound is a carboxylic acid compound.

13. A process according claim 12 in which the neutralising compound is an a-ketoacid.

14. A process according to claim 13 in which the a-ketoacid is selected from a-ketoglutaric, a-ketobutyric, a-ketoadipic, a,a1diketoadipic and pyruvic acids.

15. A process according to claim 14 in which the a-ketoacid is pyruvic acid.

16. A process according to any preceding claim in which the solution used in the neutralising step comprises isotonic saline solution.

17. A process according to any preceding claim in which an indicator is included in the solution used in the neutralising step, which changes colour upon neutralisation of all the bleaching species.

18. A process according to any preceding claim in which the solution formed in step a) has a pH in the range pH4 up to pK, of the protonated form of the bleaching species.

19. A composite product comprising a bleach activator, a peroxygen bleach source and a neutralising compound as defined in claim 1.

20. A composite product according to claim 19 comprising further an isotonic saline solution.

21. A composite product according to claim 19 or 20 having the further features defined in any of claims 6 to 15.

22. A composite product according to any of claims 19 to 21 in which the bleach source and bleach activator are included in the same composition.

23. A composite product according to claim 22 in which the said composition contains the neutraliser in delayed release form.

24. A composite product according to claim 22 or 23 in which the said composition also contains a heavy metal sequestrant.

25. A composite product according to any of claims 22 to 24 in which the said composition also contains an acidifying compound.