`
`Analyst, March 1998, Vol. 123 (503–507)
`
`503
`
`Effects of copper and zinc ions on the germicidal
`properties of two popular pharmaceutical antiseptic
`agents cetylpyridinium chloride and povidone-iodine†
`
`Jacobus J. Zeelie* and Terrence J. McCarthy
`Unit for Health Services, Port Elizabeth Technikon, Private Bag X6011, Port Elizabeth, South
`Africa 6000
`
`The effects of copper and zinc ions on the rate of killing
`of Gram-negative bacterium Pseudomonas aeruginosa,
`Gram-positive bacterium Staphylococcus aureus and
`fungal yeast Candida albicans by antiseptic agents
`cetylpyridinium chloride and povidone-iodine (Betadine)
`were investigated. In the 48 test cases copper and zinc
`ions clearly potentiated the antiseptic agents in 28 (58.3%)
`cases and exhibited an improved (not clear potentiation)
`activity in 15 (31.3%) cases. In five (10.4%) cases there
`was no change in the antiseptics’ antimicrobial activity. In
`general zinc potentiated the antiseptic agents more than
`copper. If an ‘improved activity’ was the only criterion
`for this study, then a more rapid antimicrobial effect was
`observed in 43 out of the 48 test cases, i.e., 90%.
`Keywords: Copper; zinc; cetylpyridinium chloride;
`povidone-iodine; antimicrobial; antiseptic
`
`Copper and zinc are two trace metals for which there are daily
`recommended allowances (RDA). They are also well known for
`their antimicrobial properties. Copper is commonly used as an
`antimicrobial agent in swimming pools and elsewhere whereas
`zinc is used pharmaceutically in creams, ointments, eye drops,
`etc. to combat various types of infection. In the past various
`trace metals were used quite extensively as antiseptic agents,
`but they have had to make way for more popular synthetic drugs
`such as antibiotics and other elaborate antimicrobial agents.
`These antibiotics and antiseptic agents are well known to cause
`allergies and also to allow resistance to develop in some micro-
`organisms. They are also very expensive. To overcome
`microbial resistance, doses are often increased to levels which
`simply aggravate the problems already mentioned. Alter-
`natively combinations of antimicrobial agents are not too
`infrequently employed. The consequence is all too often a
`higher incidence of untoward effects. On the other hand copper
`and zinc combinations such as the sulfates are very well tested
`and allergies are quite unknown to members of the health
`professions. In this study an attempt was made to establish if
`there exists antimicrobial interaction between these metal ions
`and two other popular antiseptic agents which are used quite
`widely because of their wide antimicrobial spectra and low
`incidence of side effects. The antiseptic agents selected were the
`quaternary ammonium compound cetylpyridinium chloride and
`the organic iodine compound povidone-iodine. The effects of
`the metal ions on these antiseptic agents were tested against a
`typical Gram-positive bacterium (Staphylococcus aureus),
`Gram-negative bacterium (Pseudomonas aeruginosa) and a
`fungal yeast (Candida albicans). All the microbial species were
`strains isolated from hospitalised patients with conditions which
`would not respond to the usual antibiotic therapy for infections
`caused by these micro-organisms.
`
`† Presented at The Sixth Nordic Symposium on Trace Elements in Human Health and
`Disease, Roskilde, Denmark, June 29–July 3, 1997.
`
`Experimental
`The concentration necessary for each of cetylpyridinium
`chloride and povidone-iodine to kill an inoculum of 1 3 106
`micro-organisms within 40 min, but not before 30 min, was
`determined. This value will be referred to as the minimum
`Increasing
`microbicidal concentration30/40 or MMC30/40.
`amounts of the metal ions were then added to each of the
`antiseptic agents and the time to kill the same number of micro-
`organisms noted. The micro-organisms were standardised
`spectrophotometrically to contain 1 3 106 micro-organisms per
`0.0001 dm3 of the culture medium.
`
`MMC30/40 determinations for the antiseptic agents
`(1) Serial dilutions were made in Normal Saline (the reaction
`medium) for each of the antimicrobial test substances. These
`were sterilised at 115 °C for 30 min in an autoclave. (2) Each
`dilution was inoculated with 1 3 106 of the appropriate micro-
`organisms and kept at 37 °C in an incubator. (3) At 10 min
`intervals and for 40 min subcultures were made into Tryptone
`Soya Broth which contained 3% m/v Tween 80 as neutralising
`agent (the recovery medium). A level of 3% m/v Tween 80 has
`been shown by several researchers1–5 to neutralise many
`antiseptic agents without inhibiting or killing the micro-
`organisms themselves. In preliminary tests this concentration
`was found to have no inhibitory effects on the test micro-
`organisms used in this study. The subcultures were then
`incubated at 37 °C for 24 h. (4) After incubation the dilutions
`were visually checked for growth (optical density).
`
`Minimum lethal concentrations for the metal ions
`This test was necessary to avoid the erroneous assumption that
`a particular antiseptic–metal ion combination killed a microbial
`population whereas the microbicidal effects may have been
`effected by the metal ions present and not necessarily a
`combination of metal ions and antiseptic agents. The test was
`essentially the same as for the antiseptic agents, but the total
`time period for subculturing was 48 h. The assumption was that
`the minimum amount which killed only after 48 h would not be
`able to kill within a time period of 40 min. The ions were used
`as sulfate salts (copper sulfate and zinc sulfate). These salts
`were soluble at the concentrations tested.
`
`Interactions
`(1) Solutions in Normal Saline containing the MMC30/40 for the
`antiseptic agents plus 5, 10, 50 or 100 3 1023 g dm3 of the metal
`ions were prepared for each antiseptic agent, for each metal salt
`and for each micro-organism. These solutions were sterilised at
`115 °C for 30 min. The stock solutions containing the antiseptic
`agents and the metal salts were sterilised to eliminate the
`presence of possible resistant extraneous micro-organisms and/
`or spores. (2) The dilutions containing the antiseptic agents and
`
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`

`504
`
`Analyst, March 1998, Vol. 123
`
`metal salts were inoculated with 1 3 106 of the appropriate
`micro-organism. (3) The inoculated dilutions were kept at 37 °C
`in an incubator. (4) At 10 min intervals 0.0001 dm3 samples
`were subcultured into the recovery medium and the latter
`reincubated at 37 °C for 24 h. (5) The subcultures were then
`visually examined for turbidity indicating microbial growth.
`The reason for choosing a reaction temperature of 37 °C is
`because the selected antiseptic agents are used on the skin and
`in body cavities where the average temperature comes close to
`37 °C.
`
`Results and Discussion
`All the micro-organisms appeared to be sensitive to both
`Betadine (which contains 1% m/v of povidone-iodine) and
`cetylpyridinium chloride (Table 1 and 2).
`The antimicrobial effects of the metals appeared to be
`particularly high against Staphylococcus aureus. This Gram-
`positive bacterium has been found in numerous investigative
`studies to be very fragile and sensitive to most antimicrobial
`agents such as antiseptics, preservatives, disinfectants, etc.,
`currently on the market. The exception, however, is antibiotics.
`Strains resistant to several antibiotics are constantly emerging in
`hospitals where many medical staff members are healthy nasal
`carriers thereof. There are currently numerous reports on the
`resistance of Staphylococcus aureus to antibiotic agents. The
`apparent resistance of the Gram-negative microbial species
`(Pseudomonas aeruginosa) is not unexpected. The resistance of
`this bacterium, especially in organic tissues, is very well
`documented. It is a bacterium which can survive on simple
`inorganic chemicals, being able to convert them to more
`elaborate organic requirements. Its ability to mutate is equally
`well documented in the literature. The reason why this micro-
`organism appears to be resistant to zinc ions, but not equally
`resistant against copper ions, could be attributed to the fact that
`zinc preparations are over-the-counter pharmaceuticals for
`which a prescription is not required. They are often applied to
`the skin or mucosa of the eye for purposes of tissue regeneration
`
`and combatting infections, whereas copper-containing prepara-
`tions are not that often used. This constant exposure of
`Pseudomonas aeruginosa to zinc may be the cause of the
`development of resistance. Pseudomonas aeruginosa is found
`on the human skin where it often infects wounds. Auto-
`infections of the eye (pink-eye infection) is also very com-
`mon.
`The information in Table 3 is important to avoid mis-
`interpretation of the observed killing effect by metal ion–
`antiseptic agent combinations (Table 4 and 5). It should be
`clearly established that the combination of agents killed the
`inoculum and not the metal ions present as the latter also exert
`an antimicrobial effect on their own.
`
`Copper
`5 3 1023 g dm23: This level of copper ions would not be able
`to kill any of the micro-organisms within a 40 min period (see
`above for minimum lethal concentrations). The killing effect of
`cetylpyridinium chloride against the yeast remained unchanged,
`but in the case of Betadine strong potentiation was evident.
`Cetylpyridinium chloride retained its original killing effects on
`Pseudomonas aeruginosa. Both antiseptic agents were po-
`tentiated against Staphylococcus aureus.
`10 3 1023 g dm23: In all instances the micro-organisms were
`killed over the whole testing period of 40 min. Since this level
`of copper could not have killed Pseudomonas aeruginosa and
`Candida albicans, a potentiated effect is obvious. The improved
`killing effect noted for Staphylococcus aureus could have been
`due to the antimicrobial properties of copper on its own against
`this micro-organism (minimum lethal concentration being 6 3
`1023 g dm23) and potentiation is therefore not clearly indicated.
`50–100 3 1023 g dm23: These levels of copper, ions in
`combination with the antiseptic agents, did not allow growth to
`take place at 5 min or longer. Once again, the improved effect
`is not necessarily potentiation as the minimum lethal concentra-
`tions for copper against all the micro-organisms are lower than
`50 3 1023 g dm23.
`
`Table 1 Minimum microbicidal concentrations30/40 (MMC30/40) at 37 °C for Betadine and cetylpyridinium chloride against three pathogenic micro-
`organisms*
`
`Antiseptic agent
`
`Betadine
`(1% m/v povidone-iodine)
`
`Time/min
`
`Cetylpyridinium chloride
`
`Time/min
`
`Pseudomonas aeruginosa
`
`Staphylococcus aureus
`
`Candida albicans
`
`Concentration
`tested (% m/v)
`3.600
`3.500
`3.488
`3.486
`3.484
`3.482
`5.038
`5.036
`5.034
`5.032
`5.030
`3.5
`3.4
`3.3
`3.2
`3.1
`
`10
`2
`2
`+
`+
`+
`+
`2
`+
`+
`+
`+
`2
`+
`+
`+
`+
`
`Concentration
`10
`tested (% m/v)
`2
`0.056
`+
`0.055
`+
`0.054
`+
`0.053
`+
`0.052
`+
`0.051
`2
`0.00040
`+
`0.00038
`+
`0.00036
`+
`0.00034
`+
`0.00032
`2
`0.0025
`+
`0.0020
`+
`0.0018
`+
`0.0016
`+
`0.0015
`+
`0.0014
`* + = Growth, 2 = no growth, & = MMC30/40 = minimum concentration which kills after 40 min, but not after 30 min.
`
`20
`2
`2
`2
`+
`+
`+
`2
`+
`+
`+
`+
`2
`+
`+
`+
`+
`
`30
`2
`2
`2
`2
`+
`+
`2
`+
`+
`+
`+
`2
`+
`+
`+
`+
`
`&
`
`&
`
`&
`
`40
`2
`2
`2
`2
`2
`+
`2
`2
`2
`2
`+
`2
`2
`2
`2
`+
`
`20
`2
`+
`+
`+
`+
`+
`2
`2
`+
`+
`+
`2
`+
`+
`+
`+
`+
`
`30
`2
`+
`+
`+
`+
`+
`2
`2
`2
`+
`+
`2
`2
`2
`2
`+
`+
`
`&
`
`&
`
`&
`
`40
`2
`2
`(+)
`(+)
`(+)
`+
`2
`2
`2
`2
`+
`2
`2
`2
`2
`2
`+
`
`Published on 01 January 1998. Downloaded on 11/03/2014 15:25:18.
`
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`
`

`

`Zinc
`5 3 1023 g dm23: This level of zinc ion on its own did not kill
`any of the micro-organisms in the absence of other antiseptic
`agents. Any improved effect noticed would therefore be due to
`potentiation. Cetylpyridinium chloride retained its original
`killing effects against Candida albicans. The effect of cetylpyr-
`idinium chloride on Staphylococcus aureus also remained the
`same. Potentiation was strong in all other test cases.
`10 3 1023 g dm23: A potentiated effect was found for all the
`antiseptic agents against Candida albicans and Pseudomonas
`aeruginosa. Since this level of metal ion could have had a
`killing effect of its own against Staphylococcus aureus, the
`improved activity throughout does not necessarily indicate
`potentiation.
`
`Table 2 Summary of the minimum microbicidal concentrations30/40
`(MMC30/40) at 37 °C for Betadine and cetylpyridinium chloride against
`three pathogenic micro-organisms*
`
`Minimum contact killing concentration30/40
`
`C. albicans
`S. aureus
`Antimicrobial agent
`P. aeruginosa
`3.200
`5.032
`3.484
`Betadine
`0.0015
`0.00034
`0.055
`Cetylpyridinium chloride
`* P. aeruginosa = Pseudomonas aeruginosa, S. aureus = Staphylo-
`coccus aureus, C. albicans = Candida albicans; MMC30/40 = Minimum
`concentration which kills after 40 min, but not after 30 min.
`
`Table 3 Minimum lethal concentrations after 48 h at 37 °C for copper and
`zinc ions against three pathogenic micro-organisms*
`
`Minimum lethal
`concentrations/
`3 1023 g dm23
`Metal ions
`
`Highest test
`concentration
`which did not kill/
`3 1023 g dm23
`Metal ions
`
`Zn++
`Cu++
`Zn++
`Cu++
`Micro-organism
`1906
`34
`1917
`36
`Pseudomonas aeruginosa
`8
`6
`9
`8
`Staphylococcus aureus
`38
`24
`39
`26
`Candida albicans
`* The above values are for the metal ions Cu++ and Zn++ (as present in
`the salts CuSO4·5H2O and ZnSO4·7H2O).
`
`Analyst, March 1998, Vol. 123
`
`505
`
`50 3 1023 g dm23: A better, improved killing effect was
`found throughout. This level of ion did kill Candida albicans
`and Staphylococcus aureus in previous studies, therefore any
`observed killing effect better than that obtained for the
`antiseptic agents on their own, should rather be described as
`improved than potentiated. Nevertheless, turbidity indicating
`microbial multiplication was only present for 5 min in the case
`of cetylpyridinium chloride against Staphylococcus aureus. In
`all of the remaining combinations potentiation was very strong
`as evidenced by the total absence of turbidity over the whole
`testing period.
`100 3 1023 g dm23: In all the cases growth was absent from
`5 min onwards. This indicates the same very strong potentiating
`effect as when 50 3 1023 g dm23 of the zinc ion was present.
`The growth observed for cetylpyridinium chloride against
`Staphylococcus aureus was completely absent.
`Several authors6–8 noticed that copper can carry certain
`substances which are extracellularly nontoxic into the microbial
`cell where they become intracellular toxins because of the fact
`that their interaction sites are inside and not on the cell. This
`effect was found to be more pronounced in Gram-positive
`micro-organisms as compared with Gram-negative bacteria. In
`this study, however, a better effect was noticed for the Gram-
`negative bacterium and this mechanism is perhaps unlikely.
`Several other mechanisms could possibly account for the
`increased killing effects found. Several investigators7,9,10
`remarked that copper can deplete microbial cells of magnesium
`and the latter is essential for protective cell wall formation. The
`metal is also known to bind with phosphate groups.11 A much
`better improvement of the overall killing effect was noticed for
`the Gram-negative bacterium as compared with the Gram-
`positive species. One should also bear in mind the possibility
`that the oversupply of any one metal may not only deplete the
`microbial cell of other metals essential for normal cell
`membrane structure and function as well as enzyme activity, but
`that it may also alter the cell’s need for other metal ions and in
`the process render the cell sensitive to damaging substances
`such as antiseptic agents or even metal ions themselves.9,12–14 It
`may be possible that excess copper could affect the zinc
`requirement for dehydrogenase enzymes and the hydrolysis of
`phosphates and peptides, all of which are found on the cell wall
`surface. Such an effect may render the cell more permeable to
`antiseptic agents and intracellular solutes. Lastly, two research
`groups15,16 proposed that polyvalent metal ions can cause
`effective charge neutralisation on microbial cells and this may
`lead to improved attachment and penetration of some antiseptic
`
`Table 4 Effects at 37 °C of copper and zinc ions on the minimum microbicidal concentrations30/40 (MMC30/40) at 37 °C of Betadine and cetylpyridinium
`chloride*
`
`Copper
`
`5
`
`10
`
`5
`
`Time/min
`
`Zinc
`
`10
`
`10
`
`20
`
`30
`
`40
`
`10
`
`20
`
`30
`
`40
`
`10
`
`20
`
`30
`
`40
`
`10
`
`20
`
`30
`
`40
`
`Metal ion concentration/
`3 1023 g dm23
`Antimicrobial agents
`Betadine—
`P. aeruginosa (3.484)
`S. aureus (5.032)
`C. albicans (3.200)
`Cetylpyridinium chloride—
`2
`2
`2
`2
`2
`2
`2
`2
`2
`2
`2
`2
`2
`(+)
`(+)
`(+)
`P. aeruginosa (0.055)
`2
`2
`2
`2
`2
`2
`2
`2
`2
`2
`2
`+
`+
`+
`+
`(+)
`S. aureus (0.00034)
`2
`2
`2
`2
`2
`2
`2
`2
`+
`+
`(+)
`+
`+
`(+)
`+
`+
`C. albicans (0.0015)
`* + Growth; 2 = no growth; (+) = faint growth; P. aeruginosa = Pseudomonas aeruginosa, S. aureus = Staphylococcus aureus, C. albicans =
`Candida albicans; MMC30/40 (appear in brackets) = minimum concentration which kills after 40 min, but not after 30 min; Note: Concentrations of 50 and
`100 3 1023 g dm23 of the metal ions allowed no growth in all test cases.
`
`+
`+
`2
`
`(+)
`(+)
`2
`
`(+)
`2
`2
`
`2
`2
`2
`
`2
`2
`2
`
`2
`2
`2
`
`2
`2
`2
`
`2
`2
`2
`
`2
`2
`2
`
`2
`2
`2
`
`2
`2
`2
`
`2
`2
`2
`
`2
`2
`2
`
`2
`2
`2
`
`2
`2
`2
`
`2
`2
`2
`
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`
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`

`

`506
`
`Analyst, March 1998, Vol. 123
`
`agents to the microbial cell. It is likely that more than one
`mechanism is involved and that the improved antimicrobial
`effects observed are the result of a combination of mechanisms.
`Zinc ions exhibited no antagonistic effect on the antimicrobial
`agents and an improved activity was observed in most of the
`combinations. Excellent potentiation was noted in several cases.
`The killing effects of zinc were mostly the same as those
`observed for copper. In the case of copper, a better killing effect
`was noted for 42 out of 48 cases, while an improved killing
`effect was found for zinc in 45 out of 48 cases. No antagonistic
`effects were observed for these two metal ions. All micro-
`organisms seemed to be affected adversely by the presence of
`copper and zinc ions. Zinc has been described as a carrier for
`oxine to obtain an improved antifungal effect.17,18 It was found
`in these studies that zinc improved the antifungal effects of the
`quaternary ammonium compounds, but not of Betadine. It is
`obvious that some sort of physical and chemical interaction
`between zinc and the antiseptic agent is of importance for this
`mechanism to apply. Zinc can displace metals such as
`magnesium7,10,19 and copper9,12–14 from microbial cells. The
`effect of magnesium depletion (as well as other metal ions) from
`a microbial cell was discussed earlier. According to this
`mechanism, Gram-negative bacteria should be more sensitive
`than Gram-positive bacteria. This was found for the quaternary
`ammonium compounds against the bacteria (not the yeast), but
`not at all for benzyl alcohol and Betadine. The charge
`neutralisation effect described for copper may hold true for zinc
`
`as well. If zinc depleted the microbial cells or other essential
`metals, copper could be one of them. Copper is involved in the
`activity of some enzymes such as oxidases.14 According to
`Eagon and Asbell,19 zinc can inhibit some step of the energy
`transfer cycle which is involved in the transport of substrates
`catalysed by magnesium. It can induce conformational changes
`in the tertiary structures of cell membrane proteins involved in
`substrate transport.
`
`Conclusion
`All the types of antiseptic–metal ion interactions observed can
`be described as follows, taking into account that (1) the
`antiseptic agents should allow microbial growth for a period of
`up to 30 min, but not 40 min, and that (2) metal ion
`concentrations above the minimum lethal levels as previously
`determined for a 48 h incubation period could have produced,
`although unlikely over a 40 min test period, an antimicrobial
`effect of their own.
`If the metal ion level is below the minimum lethal
`concentration and the possibility of an antimicrobial effect from
`the metal therefore unlikely, one can use the following as an
`indication of the degree of interaction: – – – – = excellent
`potentiation (EP); + – – – = good potentiation (GP); ++ – – =
`moderate potentiation (MP).
`If the metal ion level is above the minimum lethal
`concentration and the possibility of an anti-microbial effect
`
`Table 5 Interaction effects at 37 °C of copper and zinc ions on the minimum microbicidal concentrations30/40 (MMC30/40) of Betadine and cetylpyridinium
`chloride*
`
`Metal ion concentration/3 1023 g dm23
`
`Copper
`
`Zinc
`
`5
`
`U
`MP
`EP
`
`10
`
`EP
`IA
`EP
`
`50
`
`EP
`IA
`IA
`
`100
`
`EP
`IA
`IA
`
`5
`
`EP
`EP
`EP
`
`Antimicrobial agents
`Betadine—
`P. aeruginosa (3.484)
`S. aureus (5.032)
`C. albicans (3.200)
`Cetylpyridinium chloride—
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`U
`P. aeruginosa (0.055)
`EP
`GP
`GP
`U
`IA
`IA
`IA
`GP
`S. aureus (0.00034)
`EP
`EP
`MP
`U
`IA
`IA
`EP
`U
`C. albicans (0.0015)
`* A = antagonism, U = unchanged effect, MP = moderate potentiation, GP = good potentiation, EP = excellent potentiation, IA = improvement;
`P. aeruginosa = Pseudomonas aeruginosa, S. aureus = Staphylococcus aureus, C. albicans = Candida albicans; MMC30/40 appear in brackets = minimum
`concentration which kills after 40 min, but not after 30 min.
`
`10
`
`EP
`IA
`EP
`
`50
`
`EP
`IA
`IA
`
`100
`
`EP
`IA
`IA
`
`Table 6 Summary of the effects of copper and zinc ions on the microbial killing rates of Betadine and cetylpyridinium chloride*
`
`Copper ions
`
`Zinc ions
`
`Potentiation
`Improved action
`Unchanged
`Potentiation
`Improved action
`Unchanged
`
`Betadine
`6
`5
`1
`7
`5
`0
`
`Cetylpyridinium chloride
`5
`5
`2
`10
`0
`2
`
`Copper and Zinc
`
`13
`Potentiation
`10
`Improved action
`1
`Unchanged
`* Summary: increased killing rate (potentiation + improved action):
`No effect:
`
`+
`+
`+
`23
`1
`
`15
`5
`4
`+
`+
`
`Total
`28 (58.3%)
`15 (31.3%)
`5 (10.4%)
`43 (89,6%)
`=
`5 (10,4%)
`=
`Total: 48 (100%)
`* (Note: Quantities of 5, 10, 50 and 100 3 1023 g dm23 of each ion were tested on the above antiseptic agents’ abilities to kill Pseudomonas
`aeruginosa, Staphylococcus aureus and Candida albicans).
`
`=
`=
`=
`20
`4
`
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`
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`

`

`from the metal thus possible, although unlikely, over a 40 min
`testing period: – – – or + – – or ++ – would indicate an
`improved antimicrobial action (IA).
`If there is microbial growth for up to 30 min, but not at 40
`min: +++ – = unchanged effect (U).
`Growth throughout the 40 min testing period: ++++ =
`antagonism (A).
`The various types of interaction can now be described as one
`of the following: Excellent potentiation = EP, – – – –; Good
`potentiation = GP, + – – –; Moderate potentiation = MP, ++–
`–; Improved action = IA, – – – –/+ – – –/++ – –; Unchanged
`effect = U, +++ –; Antagonism = A, ++++. This scaling of
`responses is used in Table 5.
`Table 6 gives a summary of the antimicrobial activities of
`combinations of the various antiseptic agents with copper and
`with zinc ions. For copper ions, in general, an excellent
`improvement in the killing activity of the antimicrobial agents
`was observed in most cases. No true antagonism was observed.
`It can be seen that a more rapid microbial killing rate was
`observed in about 90% of test cases. True potentiation was seen
`in about 58% of cases and an improved action in about 31% of
`cases.
`Antimicrobial agents such as povidone-iodine (e.g., Beta-
`dine, Podine) and cetylpyridinium chloride (e.g., Savlon,
`Cetavlon) are non-specific cytotoxic agents which may cause
`untoward effects like skin or mucosal irritation, rashes and
`allergies, even at tested in-use concentrations in certain
`individuals. Copper and zinc ions in the form of the metal salts
`tested are well known for their antimicrobial properties as
`pharmaceutical agents against (bacterial, fungal, viral, proto-
`zoal) infections of the skin, eyes, etc. If small quantities of these
`metal salts can be employed in pharmaceutical formulations
`containing povidone-iodine and cetylpyridinium chloride,
`smaller quantities of the latter two agents may be used in
`pharmaceutical preparations in order to minimise the risk of
`unexpected side effects.
`
`Analyst, March 1998, Vol. 123
`
`507
`
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`Paper 7/04895E
`Received July 9, 1997
`Accepted December 4, 1997
`
`Published on 01 January 1998. Downloaded on 11/03/2014 15:25:18.
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