STEAM STERILIZATION PROCESS INDICATOR

Abstract: A steam-sensitive ink comprises, as active ingredient, a tetrazolium salt. The ink may be coated on, or impregnated into, a substrate to form a steam sterilization indicator.

Description: Title - Steam Sterilization Process Indicator This invention relates to indicator articles for use in steam sterilization processes, and to inks used in the preparation of such articles. Pressurised steam is used in hospitals to sterilize reusable medical equipment. To differentiate between a tray containing sterilised goods and one containing non-sterile goods, which may not have been processed, an indicator is used. This is typically a strip of paper with a coloured mark printed on it. The process of sterilisation causes the mark on the strip to change colour. Often the original colour is light, and the colour after processing is dark. The change in colour is caused by a chemical reaction between the steam and the ink. One of the most commonly used colour change indicators for sterilisation contains sulphur and lead salts. These compounds react under the conditions of steam sterilisation to produce lead sulphide, giving rise to a change in colour from yellow to black. Despite the widespread use and low cost of such indicators, there are several disadvantages associated with them. Firstly, the ink has a tendency to transfer to and stain articles with which it comes into contact in the autoclave. In addition to being unsightly, these stains may also contain highly toxic compounds which may be inadvertently administered to the patient. Secondly, the sensitivity of the ink diminishes with time, especially when stored in humid conditions, such that the initial and final colours may be compromised. There are numerous other colour change systems capable of detecting steam sterilisation, containing metal salts, organic acids or other compounds. Many of these are not significantly less toxic than the lead/sulphur inks, have a limited colour change, and/or are expensive. There has now been devised an indicator ink which overcomes or substantially mitigates the disadvantages associated with the prior art. According to a first aspect of the present invention, a steam sensitive ink comprises, as active ingredient, a tetrazolium salt. The tetrazolium salt used in the present invention will be a member of the class of compounds including the following general structure I: wherein X " represents an anion, and at least one of R 2 , R 3 and R 5 , which may be same or different, represents an aromatic group. Preferably, at least one, and more preferably both, of R 2 and R 3 represent aromatic groups. It is preferred that R 5 also represents an aromatic group. Aromatic groups which R 2 , R 3 and/or R 5 may represent include 5- and 6-membered monocyclic ring systems, both carbocyclic and heterocyclic, as well as fused ring systems. Examples include phenyl, naphthyl, quinolinyl, pyridyl and azolyl (eg oxazolyl, thiazolyl, benzoxazolyl, benzothiazolyl, etc). The rings may be unsubstituted, or may be substituted by one or more of a wide range of substituents. Examples of substituents which may be present are lower alkyl or lower alkoxy (ie alkyl or alkoxy with one to six carbon atoms, and which may be further substituted, eg with any of the substituents listed here), aryl groups (eg phenyl, benzyl, styryl, biphenyl, naphthyl etc), aryloxy (eg phenoxy), halogen (ie fluoride, chloride, bromide, iodide), nitro, amino, cyanide, azide, etc. Presently preferred aromatic groups which R 2 , R 3 and/or R 5 may represent include unsubstituted or substituted monocyclic groups, most preferably phenyl and oxazolyl groups. Particularly preferred compounds are those in which R 3 and R 5 both represent phenyl. Where any of R 2 , R 3 and R 5 does not represent an aromatic group, then it may represent hydrogen or an aliphatic group, eg a lower alkyl group, which may substituted with any of a wide range of substituents (eg those listed above). Furthermore, one or more of the substituents R 2 , R 3 and R 5 may act as a bridging group, connecting the tetrazolium ring to a further tetrazolium ring structure, ie the active ingredient may incorporate more than one such ring structure. For example, the active ingredient may have the general formula II: Preferred components include those in which R 2 acts as a bridge between two tetrazolium rings. In such a case, R 2 is most preferably a biphenyl group. The counterion (X ' ) can be any anion, but is preferably chloride, bromide, iodide, tetrafluoroborate, hexafluorophosphate, perchlorate or sulphate. Specific tetrazolium salts which may be mentioned include the following: 2,3,5-triphenyl-2H-tetrazolium chloride 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyl-2H-tetrazolium chloride 3 -( 1 -naphthyl)-2,5-diphenyl-2H-tetrazolium chloride 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide 2-(2-benzothiazolyl)-3-(4-phthalhydrazidyl)-5-styryl-2H-tetrazolium chloride 3,3'-(3,3'-dimethoxy-4,4'-biphenylene)-bis-(2-(p-nitrophenyl)-5-(p-thiocarbamylphenyl)-2H- tetrazolium chloride) 3,3'-(4,4'-biphenylene)-bis-(2,5-diphenyl-2H-tetrazolium chloride) 3,3'-(3,3'-dimethoxy-4,4'-biphenylene)-bis-(2,5-diphenyl-2H-tetrazolium chloride) 3,3'-(3,3'-dimethoxy-4,4 , -biphenylene)-bis-(2-(p-nitrophenyl)-5-phenyl-2H-tetrazolium chloride) 3,3'-(3,3'-dimethoxy-4,4'-biphenylene)-bis-(2,5-(p-nitrophenyl)-2H-tetrazolium chloride). Numerous other tetrazolium salts are listed in US Patent No 4,284,704. The ink of the invention preferably also comprises a binder. The binder may comprise any water resistant, heat resistant polymer. Suitable polymers include soluble polymers such as ethyl and nitro cellulose, cellulose acetate and its derivatives, hydroxypropyl cellulose, polystyrene, polymethacrylates, polyvinyl chloride, polyvinyl acetate; emulsion latexes such as polyvinylidene chloride, acrylics and polyvinyl acetate; cross-linking resins such as phenol-formaldehyde, urea-formaldehyde and melamine-formaldehyde; uv curing systems; and drying oils. Presently preferred polymeric binders include cellulose derivatives, notably ethyl cellulose and nitrocellulose. If required, a solvent may be used to provide a vehicle for the polymer. Suitable solvents for use in ink according to the invention are, for example, aliphatic alcohols, industrial methylated spirit, ethylene glycol alkyl ethers, eg ethylene glycol monoethylether, white spirit, aliphatic esters, eg isopropyl acetate, or aliphatic hydrocarbon solvents, or mixtures of two or more thereof. Water or aqueous solvent systems may also be suitable. One particularly preferred solvent is 2-ethoxyethanol. Further additives may be included to improve the coating process and the performance. Typical additives for improving coating include antifoaming agents and plasticisers. Performance can be enhanced by adding antioxidants which may be used to adjust the timing. Examples include ascorbic acid and hydroquinones. Polyhydroxybenzoic acids may be used to stabilise the system; these include the di- and tri-hydroxybenzoic acids. Addition of alkalis such as metal hydroxides, amines and guanidines may enhance the end colour and accelerate the colour change. According to a second aspect of the invention, there is provided a steam sterilization indicator comprising an ink including, as active ingredient, a tetrazolium salt, coated on or impregnated in a substrate. Substrates onto which the ink may be coated or impregnated include paper and similar materials which are permeable to steam but which maintain their integrity under steam sterilization conditions. The ink and sterilization indicator according to the invention are advantageous primarily in that they undergo a distinct colour change when subjected to steam sterilization conditions. In addition, they may be less costly and/or less toxic than known materials, and/or may exhibit greater stability. The invention will now be illustrated, by way of example only, with reference to the following Examples: Example 1 Neotetrazolium chloride* 7.5g 2,4-dihydroxybenzoic acid 12.5g ethyl cellulose 150g 2-ethoxyethanol 1 " diphenyl guanidine 1 .5g tannic acid 7.5g Example 2 Neotetrazolium chloride* 7.5g 2,4-dihydroxybenzoic acid 25g ethyl cellulose 150g 2-ethoxy ethanol U hydroquinone 12.5g Example 3 MTT** 10g Ethanol U Nitrocellulose 400g Dibutyl phthalate 5g Example 4 Blue tetrazolium chloride*** 10g 2 ethoxy ethanol u ethyl cellulose 150g 2,4,6 trihydroxybenzoic acid 20g Ascorbic acid 10g Example 5 Nitroblue tetrazolium chloride* * * * 13.5g Ethyl cellulose 168g 2-ethoxyethanol U Hydroquinone 2.2g 2,4-dihydroxy benzoic acid 101g Tannic acid 13.5g * Neotetrazolium chloride = 3,3'-(4,4'-biphenylene)-bis-(2,5-diphenyl-2H-tetrazolium chloride) ** MTT = 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium chloride *** Blue tetrazolium chloride = 3,3-(3,3'-dimethoxy-4,4'-biphenylene)-bis-(2,5-diphenyl-2H-tetrazolium chloride) **** Nitroblue tetrazolium chloride ■ = 3,3'-(3,3'-dimethoxy-4,4'-biphenylene)-bis-(2-(p-nitrophenyl)-5-phenyl-2H-tetrazolium chloride) For each formulation, the components were mixed together and dissolved, then deposited on a paper substrate either by coating or printing.

Claims: Claims 1. A steam sensitive ink comprising, as active ingredient, a tetrazolium salt. 2. An ink as claimed in claim 1 , wherein the tetrazolium salt is a member of the class of compounds including the general structure I: wherein X " represents an anion, and at least one of R 2 , R 3 and R 5 , which may be same or different, represents an aromatic group. 3. An ink as claimed in claim 2, wherein at least one, and more preferably both, of R 2 and R 3 represent aromatic groups. 4. An ink as claimed in claim 3, wherein R 5 also represents an aromatic group. 5. An ink as claimed in any one of claims 2 to 4, wherein the aromatic groups which R 2 , R 3 and/or R 5 represent are selected from the group consisting of 5- and 6-membered monocyclic ring systems, both carbocyclic and heterocyclic, and fused ring systems. 6. An ink as claimed in claim 5, wherein the aromatic groups are selected from the group consisting of phenyl, naphthyl, quinolinyl, pyridyl and azolyl. 7. An ink as claimed in any one of claims 2 to 6, wherein the aromatic groups are unsubstituted, or are substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, aryl groups, aryloxy, halogen, nitro, amino, cyanide, and azide. 8. An ink as claimed in any of claims 2 to 7, wherein R 2 , R 3 and/or R 5 represent phenyl or oxazolyl groups. 9. An ink is claimed in any one of claims 2 to 8, wherein R 3 and R 5 both represent phenyl. 10. An ink as claimed in any preceding claim, wherein the active ingredient is of the general formula II: 11. An ink as claimed in claim 10, wherein R 2 is a biphenyl group. 12. An ink as claimed in any one of claims 2 to 11 , wherein X " represents a counterion selected from the group consisting of chloride, bromide, iodide, tetrafluoroborate, hexafluorophosphate, perchlorate and sulphate. 13. An ink as claimed in claim 1, wherein the tetrazolium salt is selected from the group consisting of 2,3, 5-triphenyl-2H-tetrazolium chloride; 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyl-2H-tetrazolium chloride; 3-(l -naphthyl)-2,5-diphenyl-2H-tetrazolium chloride; 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; 2-(2-benzothiazolyl)-3-(4-phthalhydrazidyl)-5-styryl-2H-tetrazolium chloride; 3,3'-(3,3 , -dimethoxy-4,4'-biphenylene)-bis-(2-(p-nitrophenyl)-5-(p-thiocarbamylphenyl)-2H- tetrazolium chloride); 3,3'-(4,4'-biphenylene)-bis-(2,5-diphenyl-2H-tetrazolium chloride); 3,3'-(3,3'-dimethoxy-4,4'-biphenylene)-bis-(2,5-diphenyl-2H-tetrazolium chloride); 3,3'-(3,3'-dimethoxy-4,4 , -biphenylene)-bis-(2-(p-nitrophenyl)-5-phenyl-2H-tetrazoliumchloride); and 3,3'-(3,3 , -dimethoxy-4,4'-biphenylene)-bis-(2,5-(p-nitrophenyl)-2H-tetrazolium chloride). 14. An ink as claimed in any preceding claim, further comprising a binder. 15. An ink as claimed in claim 14, wherein the binder is selected from the group consisting of ethyl and nitro cellulose, cellulose acetate and its derivatives, hydroxypropyl cellulose, polystyrene, polymethacrylates, polyvinyl chloride, polyvinyl acetate; emulsion latexes such as polyvinylidene chloride, acrylics and polyvinyl acetate; cross-linking resins such as phenol- formaldehyde, urea-formaldehyde and melamine-formaldehyde; uv curing systems; and drying oils. 16. An ink as claimed in claim 15, wherein the binder is a cellulose derivative. 17. An ink as claimed in any preceding claim, further comprising a solvent. 18. An ink as claimed in claim 17, wherein the solvent is selected from the group consisting of aliphatic alcohols, industrial methylated spirit, ethylene glycol alkyl ethers, white spirit, aliphatic esters, aliphatic hydrocarbon solvents, water, and mixtures of two or more thereof. 19. An ink as claimed in claim 18, wherein the solvent is 2-ethoxyethanol. 20. A steam sterilization indicator comprising an ink as claimed in any preceding claim, coated on or impregnated in a substrate. 21. An indicator as claimed in claim 20, wherein the substrate is of paper or similar material which is permeable to steam but which maintains its integrity under steam sterilization conditions.

Inventors: JAMES PHILLIP RICHARD, JAMES, PHILLIP, RICHARD
Applicants: BROWNE ALBERT LTD, ALBERT BROWNE LIMITED
Application year: 1998
Main classification: C09D11
IPC codes: A61L2, C09B50, C09D11, C09K9, G01N31