PROCESS FOR PREPARING BACTERICIDAL MATRICES
The present invention relates to a process for preparing bactericidal matrices. The present invention also relates to bactericidal articles formed from the matrices. The matrices may be moulded in numerous shapes so as to replace, or cover, everyday items and equipment which are handled by numerous people. Examples of typical everyday items include door handles, door touch plates, lavatory handles, lavatory seats and telephone handsets. These are hereafter referred to as "touch related products".
One of the major problems associated with touch related products in today's society . is the spread of cross infection. Most household or office items that are constantly being touched by human hands are made from plastics materials and rubber materials. These materials tend to harbour and accumulate dirt and germs if they are not cleaned properly and on a regular basis. If dirt and germs do accumulate, so the spread of diseases and illnesses increases.
It is therefore not unusual for large organisations to employ specialised firms to clean their office equipment etc. on a regular basis. " However, this is an expensive exercise. It is one object of the present invention to do away with this cleaning requirement and at the same time to provide items that are more hygienic and pleasant to use.
Up until to date, the only effective way to remove any unwanted germs, such as bacteria, is to wipe the items with a disinfectant. When the disinfectant is applied in this matter, it behaves as a bacteriostatic agent (i.e. it hinders growth of bacteria) and as a bactericidal agent (i.e. it kills bacteria) .
However, disinfectants can only normally work in a wet environment. Accordingly, when the applied disinfectant dries, the disinfectant (and thus also the item to which it has been applied) loses its bacteriostatic and bactericidal properties. It is necessary therefore to keep wiping the items with disinfectant to prevent the build up of germs. Clearly this is not a practical solution to prevent the spread of cross infection.
Over the past 50 years or so, there have been a number of attempts by the hygiene industry to prepare a plastics material or the like that displays both bacteriostatic and bactericidal properties. By way of example, some disinfectants have been sprayed onto or incorporated within some plastics materials. This has proved to be an unacceptable solution because if the disinfectant becomes neutralised, the bacteria start to multiply again, thus promoting the spread of cross-infection.
The prior art is replete with suggestions for making antibacterial materials, and many of the prior art disclosures relate to shields for use on telephone handsets. Such shields have been made out of materials such as rubbers, plastics, metals and crepe or corrugated paper. Examples of such disclosures are US-A-3,169,171, US-A- 4,570,038, US-A-2,080,676, US-A-2,28S ,975 and GB-B- 2,119,203. Such antibacterial materials only have a bacteriostatic effect. They do not display any bactericidal properties.
For instance, US-A-4,570,038 discloses a set of shields for use on telephone handsets, the set comprising a sound permeable plastics element having a bacteriostat, such as 10,10 oxybisphenoxarsine (OBPA), impressed into the plastic element. The bacteriostat does not diffuse out from the shields. With these shields, bacteria and the like are prevented from growing within the shield.
It is apparent that the shields of US-A-4,570,038 have a number of disadvantages. First, only a bacteriostatic agent is impressed into the plastics matrix of the shields. Accordingly, the added agent cannot kill bacteria and the like. Instead it merely inhibits the growth rate of bacteria. Secondly, the bacteriostat is only effective within, and not on the surface of, the plastics matrix of the shields. Accordingly, the agent will only protect, and to a limited degree, the interior of the shields from bacterial attack, thereby preventing internal "pink staining" or cracking. It is therefore still possible for bacteria to grow on the exterior surfaces of the shields and be transferred to the user.
Ideally, therefore, if an article is to prevent the spread of diseases and illnesses, it must exhibit a bactericidal property on its surface.
In the prior art there are some reported attempts for preparing bactericidal shields, such as the shields disclosed in GB-A-2,180,752 and EP-A-0,262,921.
GB-A-2,180,752 discloses a set of bactericidal shields for use on telephone handsets, the set comprising a pair of plastic shields designed to clip over or into the telephone mouthpiece or earpiece respectively, each shield being impregnated with a bactericidal agent which is said to be able to diffuse out of the shield over a period of time.
In GB-A-2,180,752 it is specified that the bactericidal agent is impregnated into the shields (i.e. the agent is not bound to the plastics material) . The disclosure of GB-A- 2,180,752 is typical of many prior art disclosures in that it does not contemplate any method for endowing the shields with bacteriostatic and bactericidal properties other than impregnation.
Moreover, it appears that, contrary to the desire of the inventor, the bactericidal agent impregnated into the shields does not diffuse out over a reasonable period of time. The shields are, therefore, ineffective in preventing the spread of cross infection.
EP-A-0,262,921 discloses a set of bactericidal shields for use on telephone handsets. The shields comprise a rigid polyvinylchloride or rigid polystyrene formulation containing a bactericidal agent, such as a heterocyclic or halogenated cyclic bactericidal agent, e.g. Ultrafresh (Ultrafresh, which is supplied by Thomson Research Associates, is a trade mark) . On moulding the formulation, the bactericidal agent is allegedly incorporated into the molecular structure of the plastic and the formulation is activated.
It has been found that the shields described in EP-A- 0,262,921 do not meet the object of the present invention. In particular, because the bactericidal agent is in¬ corporated into the molecular structure of the plastics matrix, the agent cannot diffuse out of the matrix. Thus, these shields, like other prior art shields (e.g. those of GB-A-2,180,752) are ineffective on the surface of the shield and remote from the surface of the shield. Moreover, these shields, like the other prior art shields, are only really bacteriostatically effective against gram positive bacteria such as Staph. Aureus. They do not have any significant bacteriostatic effect against gram negative bacteria such as E. Coli.
It is therefore an object of the present invention to overcome, at least to some extent, these disadvantages by providing a process for preparing a matrix that exhibits a bactericidal effect that can last for at least 30 days against both gram positive and gram negative bacteria.
In a first aspect, the present invention provides a method for producing a bactericidal matrix which comprises mixing a support matrix with an alkylated diaminoalkane-type antibacterial agent and an organoarsenic-type antibacterial agent, and optionally moulding the mixture obtained.
In a second aspect, the present invention provides a bactericidal matrix comprising a support matrix, an alkylated diaminoalkane-type antibacterial agent and an organoarsenic-type antibacterial agent.
For both the process and the bactericidal matrix, typical matrices include plastics-type support matrices, paints, paper, rubber etc. The term "plastics-type support matrices" means any natural or synthetic plastics, such as polyvinylcholride (PVC) and polyethylene (PE) , and thermoplastic rubbers such as butadiene-based block copolymers and natural rubbers.
Preferably, the combined amount of the alkylated diaminoalkane-type antibacterial agent and the organoarsenic antibacterial agent comprises between 0.05% and 7% of the formulation. (In the present specification, all the quantities and percentages for the components of the process and bactericidal matrix will be expressed by weight of component in the total bactericidal matrix, unless otherwise stated) .
Advantageously, the combined amount of the alkylated diaminoalkane-type antibacterial agent and the organoarsenic antibacterial agent comprises between 0.2% and 2% of the formulation.
Preferably, the alkylated diaminoalkane-type antibacterial agent is l-alkylamino-3-aminopropane, wherein the alkylamino group is a primary or secondary amino group and the alkyl group is a straight or branched chain alkyl group.
Conveniently, the organoarsenic antibacterial agent is added to the mixture while absorbed on a polymer carrier, preferably in the form of granules. Suitable corners include PVC and polystyrene. Advantageously, the moulding composition contains 1 to 20% of the organoarsenic agent in
PVC. A suitable formulation contains 1 to 20%, preferably
5%, OBPA in PVC. One such formulation is Vinyzene SB1PS
(Vinyzene, which is supplied by Morton Thiokil Inc.,is a trademark) . Alternatively, the organoarsenic antibacterial agent may be added as a liquid.
Preferably, the organoarsenic antibacterial agent is an aromatic arsenic compound. Most preferably, the organoarsenic antibacterial agent is either a phenarsazine chloride or a phenoxarsine, such as 10, 10 oxybisphenoxarsine (OBPA) .
Advantageously, the alkylated diaminoalkane-type antibacterial agent is added to the mixture in the form of an oil based solution. The oil base may be coconut oil, linseed oil, rape seed oil, or corn oil. A typical mixture is an oil based solution comprising from 5 to 30% of the alkylated diaminoalkane-type antibacterial agent.
A preferred plastics-type support matrix is a styrene- butadiene block copolymer, such as Styrolux (Styrolux is a Registered Trade Mark of BASF AG) .
Preferably, if the matrix is to be moulded, it is moulded by vacuum forming or injection moulding to a shape that can replace, cover, fit over or fit into any touch related product. For example, the matrix may be moulded to a shape to fit over or into any household or office touch related product such as a door knob, a door touch plate, a lavatory handle, a telephone mouthpiece or an earpiece of a telephone handset.
Advantageously, a set of moulded matrices can be provided, such as a set of bactericidal matrices for use on telephone handsets. Moreover, the sets can be provided in kit form.
A preferred composition comprises 97% Styrolux, 1% Vinyzene SB1PS and 2% of a coconut oil base containing 10% 1- alkylamino-3-propane, yielding a final concentration of 1- alkylamino-3-aminopropane of 0.2% and a final amount of OBPA of 0.05%. The concentration of the l-alkylamino-3- aminopropane and OBPA in the moulded articles are within the approved levels set by the US Environmental Protection Agency. It has been found that even at these low levels of antibacterial agents, the matrices of the present invention are bactericidally effective against both gram positive and gram negative bacteria.
It has been noted that a mixture comprising a plastics type matrix and either one of the antibacterial agents alone has substantially no bactericidal activity with respect to gram negative bacteria, and minimal bactericidal activity with respect to gram positive bacteria, even though an antibacterial agent is mixed in the composition. In light of this, it is surprising that the matrices of the present invention have bactericidal properties against both gram positive and gram negative" bacteria.
In matrices comprising both the antibacterial agents, the agents seem to act synergistically, thus enabling the matrices to show bactericidal activity. The mechanism of this synergistic activation is at present unknown. However, it has been shown that the matrices of the present invention are bactericidal, not merely bacteriostatic, and that the bactericidal activity also extends remote from the surface of the article.
It is conjectured that the combination of the two antibacterial agents with the support matrix enables the 1- alkylamino-3-aminopropane to diffuse out of the support matrix and thus exert its bactericidal effect remote from the walls of the bactericidal matrix.
The bactericidal matrices of the present invention have good bactericidal properties which can last up to 30 days or more and which extends not only to the immediate area of the shield but also to a "halo" area around it.
The synergistic effect of the two antibacterial agents is particularly noticed where the matrices are in the form of moulded articles formed, for example, by vacuum forming or injection moulding.
In addition to the antibacterial agents, one or more of a germicidal agent, an algaecidal agent, a fungicidal agent, a biocidal agent, and anti-dandruff agent or a perfume may be included in the bactericidal matrices or articles. These are preferably mixed into the composition during the process stages.
It is particularly preferred that a perfume such as a lemon, pine or rose aroma be included in the matrices. Conveniently, the bactericidal matrices include a substance which changes colour when a predetermined reduction in the activity of the agents in the shield has occurred, or after the lapse of a predetermined time, thereby providing a ready indication as to when the article should be changed.
Preferably, the colour indicator is in the form of a icrodot or a microdot matrix affixed to, applied to or incorporated in the article. The colour indicator could, for instance, change to red or could make visible a word such as "now" when the colour change occurs. Preferably, the substance which changes colour is a substance which is sensitive to ultraviolet or visible light.
If the bactericidal matrices are moulded to a particular shape (e.g. to fit over an office touch-related product) , the moulded matrices (otherwise called bactericidal articles) may be adapted or formed so that they are readily removable when the bactericidal activity of the bactericidal articles has been substantially exhausted. The bactericidal articles will thus be disposable.
The bactericidal articles according to the present invention can be supplied in packages to cleaning contractors who could merely change the articles, for instance, at monthly intervals. This would represent a considerable cost and manpower saving compared to the normal cleaning operation which needs to be carried out at least weekly.
If the article is to be moulded as a protective cover, such as a shield for a telephone handset, the cover will generally be between 0.25 and 0.50, preferably 0.30 and 0.38, millimetres in thickness.
If the article is to be used as a shield for use on a telephone handset, the shield may be perforated to match the perforations of the mouthpiece and earpiece respectively of the telephone handset. Alternatively, the holes in the shield may be offset with respect to the holes in the handset so as to reduce further the ingress or collection of dirt and/or germs.
It may not be necessary for the shield to be perforated since the shield without perforations is still able to transmit sound without significant distortion. The shield may come in many different shapes and sizes so as to be able to fit any type of telephone handset.
Preferably, a plurality of articles according to the invention are provided for sale packed in a suitable moisture-proof carton, with each article being individually
sealed in an evacuated, sterile plastic or foil container. The carton could be kept by its respective touch related product, thereby allowing the user to change the article at will.
The bactericidal articles according to the present invention, as well as displaying good bactericidal properties, have further advantages over the articles of the prior art. For example, they can be moulded to fit tightly around or within any common household or office item without the need for extra catches, flanges, ribs, clips or other mounting means or moving parts. Moreover, they do not include any lint, gauze, paper, card, filters or cloth and they are not impregnated, dipped, coated, laminated or glued. They are therefore very simple to prepare and use. Nonetheless, they are highly effective, and produce a bactericidal effect not only on their immediate surface, but also in a "halo" area around them.
The present invention is now described, by way of illustration only, in the following two Examples.
Example A
A composition comprising Krayton rubber, OBPA and 1- alkylamino-3-aminopropane was prepared by mixing the components in a conventional rubber mixer. The OBPA was added in the form of Vinyzene SB1PS pellets, a formulation comprising 5% OBPA in polystyrene. The l-alkylamino-3- aminopropane was added as a solution in coconut oil, the solution containing 10% l-alkylamino-3-aminopropane. The final composition contained 0.05% OBPA and 0.2% 1- alkylamino-3-aminopropane as the active ingredients.
The formulation was injected moulded at a temperature of approximately 200°C and at a pressure of approximately 160 Kg/cm for 8 seconds to form sets of articles 0.30 millimetres thick.
When tested, it was found that these articles were highly bactericidal. The bactericidal activity wad not limited to the immediate area of the articles, but extended also to a "halo" area around the article. The testing is described below.
Testing Procedure
In the testing procedure, the bactericidal activity of the articles according to the present invention (PS) was compared against a control article prepared from Krayton alone (SK) . The control articles was prepared in a similar manner to that described above.
A bactericidal test (see Experiment A below) was then performed on the bactericidal article of the present invention (PS) and on the control article (KS) .
Experiment A Procedure
Agar plates were flooded with an overnight culture of bacteria containing S. Aureus (ATCC6538) and E. Coli
(ATCC11775) . Excess inoculum was then removed from the surface of the plate and the surface of the agar was allowed to dry for 20 minutes at 27°C.
A small piece of each article to be tested was placed independently onto the surface of the seeded agar. The articles studied included bactericidal articles according to the present invention (PS) and the control article (KS) .
Each plate was incubated at 37°C. After 24 hours of incubation, each plate was examined for evidence of growth- free zones (i.e. "halo"-effect) around each piece of article for both S. Aureus and E. Coli.
Results
Growth-free zones (mm) 24 hours Article S. Aureus E. Coli
KS 0 0
PS 4 2.5
Conclusion
The bactericidal article according to the present invention exhibits excellent bactericidal properties.
Example B
A composition comprising Styrolux, OBPA and l-alkylamino-3- aminopropane was prepared by mixing the components in a conventional plastics mixer. The OBPA was added in the form of Vinyzene SB1PS pellets, a formulation comprising 5% OBPA in polystyrene. The l-alkylamino-3-aminopropane was added as a solution in coconut oil, the solution containing 10% l-alkylamino-3-aminopropane. The final composition contained 0.05% OBPA and 0.2% l-alkylamino-3-aminopropane as the active ingredients.
The formulation was injected moulded at a temperature of approximately 200°C and at a pressure of approximately 160 Kg/cm for 8 seconds to form sets of articles 0.30 millimetres thick and shaped so as to be able to fit over the mouthpiece and earpiece of a conventional telephone handset. When tested, it was found that these articles were highly bactericidal and retained their activity for 30 days or more. The bactericidal activity was not limited to the immediate area of the shields, but extended also to a "halo" area around the shield. The testing is described below.
Testing Procedure
In the testing procedure, the bactericidal activity of the articles according to the present invention (PS) was compared against four control articles.
The control articles were prepared from: Styrolux alone (SS) ;
Styrolux containing OBPA (OS) (final concentration of OBPA being 0.05%);
Styrolux comprising l-alkylamino-3-aminopropane (AS) (final concentration of l-alkylamino-3- a inopropane being 0.2%); and Styrolux comprising Ultrafresh (US) (final concentration of Ultrafresh being
0.2%) . (Ultrafresh is a Trade Mark of Thomson Research Associates and contains halogenated and heterocyclic antibacterial agents) .
The control shields were prepared in a similar manner to that described above.
Three types of experiment (experiments IB, 2B, and 3B) were then performed on the bactericidal articles of the present invention and on the four control articles.
Experiment IB Procedure
A bactericidal article according to the present invention (PS) and a Styrolux control shield (SS) were each attached with tape to a respective telephone handset mouthpiece. After five days normal use of the telephone handsets, the articles were removed. After removal, the articles were firmly pressed into nutrient agar (NA) and into yeast medium agar (YM) , each contained within sterilised petri plates.
The agar plates were incubated at 28°C for five days to allow adequate time for the growth of any viable micro¬ organisms. The nutrient agar encourages growth of bacteria, whereas the YM agar encourages growth of fungal species.
Results
Article Number of organisms recovered
NA YM
PS 3 2
SS (Control) 48 52
% reduction in 93.8% 96.2% number of organisms
Discussion
The results showed that the shields according to the present invention (PS) possess excellent antimicrobial properties, as the number of viable organisms recovered from the PS article was less than 10% of the number recovered from the SS control article.
Experiment 2B Procedure
A 24 hr culture of S. Aureus (ATCC 6538) was sprayed onto the surface of a bactericidal article according to the present invention (PS) and a Styrolux control article (SS) . The shields were incubated at 36°C. Samples were then removed at 90 minutes and 24 hours. Each respective sample was added to 25ml of a sterile broth. The broth mixture was stirred and an aliquot of the mixture was then spread over individual agar plates. The plates were stored at 35°C to 37°C for 90 minutes and for 48 hours. Bacterial counts were then conducted by standard methods.
Results
Bacteria count per article Sample time PS shield SS control
90 minutes 240,000 1,300,000 48 hours 25* 25,000,000
(* none detected)
Conclusion
The testing indicates that at a period of 48 hours virtually all of the bacteria have been killed by the articles according to the present invention.
Experiment 3B Procedure
Agar plates were flooded with an overnight culture of bacteria containing S. Aureus (ATCC6538) and E. Coli (ATCC11775) . Excess inoculum was then removed from the surface of the plate and the surface of the agar was allowed to dry for 30 minutes at 37°C.
A small piece of each article to be tested was placed independently onto the surface of the seeded agar. The articles studied included bactericidal articles according to the present invention (PS) and the aforementioned four control articles (i.e. SS, OS, AS and US).
Each plate was incubated at 37°C. After 24 hours of incubation, each plate was examined for evidence of growth- free zones (i.e. "halo"-effect) around each piece of article for both S. Aureus and E. Coli.
Results
Growth-free zones (mm) 24 hours
Article S. Aureus E. Coli
SS 0
AS 0
OS 4 1
US 2 . 5 0
PS 6 3
Conclusion
The bactericidal matrices and articles according to the present invention exhibit excellent bactericidal properties.
It is further apparent that, because the articles comprising the support material (i.e. just Styrolux) and l-alkylamino- 3-aminopropane do not exhibit any bactericidal properties, there is a synergistic effect between the OBPA and l- alkylamino-3-aminopropane when incorporated in the support material. In this regard, it is believed that the OBPA binds to the backbone of the support material and that the l-alkylamino-3-aminopropane is carried on the bound OBPA. This appears to allow the l-alkylamino-3-aminopropane to diffuse out of the article over a period of some 30 days or more.
It will, of course, be understood that the present invention has been described above purely by way of example, and that modifications of detail can be made within the scope of the invention.