AU463533B2 - Antibacterial activity and compositions therefor - Google Patents

Description

4.2 1 6 0 n72

the control of This invention relate-, to bacteria. invention we provide According to the present activity of an a method of improving the comprises adding to antibacterial compound which a surface-active agent the? antibacterial compound perfluorflcarbon contailifl a terminal aliphatic c arbon atoms and a group of at least three hydrophilic group. of the present According to another aspect and improved invention we provide novel comprising a compound. antibacterial compgsitions

463.53 3 havin antibacterial 4a2c1 aivi 6 0and n2 a surface-active agent containing a terminal/'prfluorocarbon group of at least three carbon atoms and a hydrophilic group.

The fluorocarbon surface-active compounds

accelerate the activity of mainy bactericides and

bacteriostats for example phenolic compounds,

alky! ammonium compounds, diguanido alkanes,

hypochlorites, chloramines, acridines, hydroxy

quinolines, aminotriphenyl methanes. The present

invention is especially applicable to the addition of the fluorocarbon surface-active compounds as

described herein to phenolic compounds, alkyl

ammonium compounds, and diguanido alnes a. salts tthreof The phenolic compounds which may be used as

antibacterial compounds include phenol itself,

chlorophenols and phenyl phenols. A range of

chlorophenols may be used depending on the number

of chlorine atoms present in the phenolic rinn

and the presence or otherwise of other substituents,

but phenyl chlorophenols and chloroxylenols are

preferred. A range of phenyl phenols may be used

depending on the position occupied in the phenolic ring by the phenyl substituent. It is especially preferred to use phenol,

orthophenyl orthochlorophenol (which may be admixedwith

orthophonyl parachlornphienol), 4-chloro-,5-xylenol and

463.533

4.2160 n2 orthophenyl phenol as the antibacterial compounds. 'Alkyl ammonium compounds which may be used as

the antibacterial compounds include cetyl mothyl

ammonium halides, for example cetyl trimethyl

ammonium bromide and cetyl dimethyl ammonium

chloride, and cotyl pyridinium halides.

Diauanido alkanes which may he used as the

antibacterial compounds include 1,6-di(phenyl

diguanido) hexanes, for example 1,6-di(4-chloro-

phenyl diguanido) hexane, and salts thereof.

Other specific compounds for which

bactericidal activity is markedly accelerated by

the addition of fluorocarbon surfactants include

pine-oil and beta-phenoxyethanol. The fluorine-containing surface-active agent

may be any compound containing a hydrophilic group

and a terminal aliphatic perfluorocarbon group of

at least three carbon atoms. The perfluorocarbon

group of at least three carbon atoms may be either

the whole or part only of the fluorocarbon portion

of the molecule. Thus the perfluorocarbon group

may be the whole of or a part only of a branched

or a straight perfluoroalkyl or perfluoroalkenyl

group. Groups containing hydrogen atoms may be

intervening between the said terminal perfluoro-

carbon group and the hydrophilic part of the

molecule.

463.533

4.2 16 0/n2 group of three or more The perfluorocarbol

carbon atoms may be a perfluoroisopropyl or' preferably pe-rfluorotertiarybutyl group, but it is

a group containing a terminal chain portion of at

thr~e carbon atoms, for oxamplo a t4'rm inal ltoast

portion of a straight perfluoroalky] chain

CF (CF)n or a terminal portion of oither branche~d

perfluorealkenYl or perfluoroalkyl chains of which

the following are preferred examples:

(CF 3 2 CF(CF 2 n

(CF CC C CF- 2(F3 2 5) CF 3 2 F) 3(

C2F5 -C(CF 3 C(CF3 CF2 -F2

(C2 F5 2 -C(CF 3 C112

(C 2 F5 2 -C(CF 3 CII C(CF 3

The hydrophilic group may be ionic or non-ionic

and in the case of ionic groups, which in general both will consist of anion-c ation pairs, either or

ionic groups may be attached covalently to the

fluorocarbon part of the molecule. The hydrophilic

group preferably is a group which exerts a powerful

wae-oublsn effect on the whole molecule.

The stir acv-activo aciont may contain more than

onev anionic, .c-a iocni c, amphoter ic or non-ionic

group which may be of the same or hydrophilic

different types.

463,533

4.2 16 0 n2 Suitable surface-active agents of the anionic

type include those in which the hydrophilic group

is a carboxylate, phosphate, phosphonate or

sulphonate, for example alkali-metal and alkyl

ammonium salts of perfluorocarboxylic,

per Iluorophosphoric and perfluorosulphonic acids.

Suitable non-ionic surface-active agents

include those in which the hydrophilic group is an

oxyalkylene chain containing an oxygen/carbon ratio

greater than 0.3.

Suitable compounds of the anionic and non-ionic

type include compounds having the formulae

R OC6 ISO3-M

R fO(CH2CI20 )xR

RfO(CH2 CH20 )xRf

R OC6H4CH20(CH 2CH'20) xR

wherein Rf is C F2n+ or C F 2n-1 straight-chain or branched-chain, the branched-chain being

preferably derived from oligomers of

tetrafluoroethylene (C 2 F4 n where n 4, 5 or 6

M is alkali-metal or ammonium

R is hydrogen or short alkyl C 1 -C6 x is an integer 1 to

Especially suitable compounds are cationic

surface-active agents in which the hydrophilic

group is a quaternary nitrogen group, the quaternary

nitrogen cationic centre being attached covalently

463.533

4,2 16 np0 The preferred to the perfluorocarbon group. containing cationic surface active agents arc those grou.ps. The alkyl ammonium groups and pyridilniuf activity compounds may not have marked bactericidal

themselves but the synergistic increase of the

very activity of an antibacterial compound is

marked.

Preferred compounds containing quaternary

nitrogen cationic groups include the following

types of compound:

RfC1CH 2C NR A

R CH2CH N(Z)R 2 A A R fC6114SO2NR (CH )mNR3

R fOC 6 H4 C 2 NR 3 A +4 R OC 6 H4 CH 2 NR 2 CH 2 CH 2 COO

RfNH-(CH2)mN(Z)R 2 A-

R fOC6 H4 CH 2 N(Z)R 2 A

RfSO 2 NR(CH 2 3 NR 3 A-

wherein Rf and R are as defined above

m is an integer 1 to 6

Z is a long.alkyl C 1 0 -C 2 0

A is an anion

and compounds of the type

R (HF)O(C5 H 4 N)R A-

and R O(C54N)R A-

wherein R C F 2 n_ and R and A are as defined above.

463.533

4.2160/12 include Esp,?c ially prefer red compound,;

9 (CHi A- R f OC 6 1 4 SO 2 NH(CII 2 3 3 3

rl f Oc 1f 4 Cl 2 5 A- 6

and R fo(C 5 114 )CHI3 A-

wherein Rf is a C P5 0F1 or C 12F2

and A is Cl, Br, I or C11 3 so 4

of m~ny of the The methods of preparation or listed above surface-active agients described

hlave been published in our UK Patent Specifications

1,148,486; 1,17(,492; 1,270,661; Nos. 1,130,822;

1,270,662; and 1,270,838.

463.533

4.2 16 0 n2 The preparation of a compound of the type RfO(CSH 4 N)CH 3 A- may be performed by reacting a perfluoroolefine R f with a hydroxy pyridine followed by quaternising the resulting pyridine compound having

the general formula RfO(C 5 H 4 N) with appropriate

reagents, for example dialkyl sulphates, alkyl

halides and alkyl esters of aryl sulphonic acids.

When the fluorocarbon surface-active agents described hereinbefore are added to a bactericidal

composition, the rate of killing of bacteria may be

observed .to increase. Increases in rate of kill for example from 50% to 500% may be observed from

the addition of fluorocarbon surface-active agent

to the aforesaid bactericides in proportions at

concentrations for example in the range from 10:1

to 0.001:1 measured as weight of fluorocarbon

463.533

4216o0 2 compound to weight of aitibacterial compound,

preferably 5:1 to 0.01:1 and especially 2:1 to 0.1:1. The acceleration of bactericidal or

antibacterial activity may be useiXul inantistptic

compositions containing phcnolic compounds, alkyi

ammonium compounds, diguanido alkanos and other

bactericides, for example as used for the external

dressing of wounds, disinfectants for household,

industrial, agricultural or hospital use, and in

compositions having activity in addition against

organisms other than bacteria, e.g. viruses,

spores, slimes and algae.

In many cases for example bactericides of the

class of oxines or acridines may be rendered effective against a wider range of bacteria. Thus

for example some bactericides a benzalkonium

halide) are active only against bacteria of the

gram-positive group but the addition of a fluorocarbon

surfactant will extend their activity to include bacteria of the gram-negative group.

The invention is illustrated but in no way

limited by the following Examples in which the

parts and percentages are by weight unless

otherwise stated, and in which the following

eleven chemical surfactants were used:

4 63. 533

4.2 1-6 0 n2 1. C 10 F 1C9C 6 f4 CH 2 A (C 2 H5 3 I (FCS1) 2. C 10F 0C C19 I so Na+ (FCS2)

3. C10 1 9 0C 6 114 so 2 m (C 2 3 (Cu 3 3 C11 3 SU 4 (FCS3)

4. C 1 0 F 1 9 OC 6 H4 C 2 (C 2 H 5 3 Cl- (FCS4)

C8 1 7 s 121 (CH2 3N (CH 3 1-

6. C8F150C 6H4s I C (CH 3 3 CH 3 S0 4 (CS6)

7. C F OCc C.1) 1 .(FCS7) 8. C8 1 5 OC C114 C 5 IY I- (FCS8)

9. C8F1 50 (C 5 li)4 C1[ 3 C113 S0 4 (FCS9)

C 1 0 F 1 90 (C H CH3 CH3S04

11. C 12 F 23 0 (C 5 4 CH 3 CH 3 SO 4 (FCS11)

Example 1

Four representative micro-organisms were selected

for bacteriological tests namely:

Staphylococcus aureus

Proteus vuigaris

Pseudomonas aeruginosa

Escherichia coli

and each of these were prepared as a standard

innoculum.

The bactericidal activity of phenol to each

of these micro-organisms was established by adding

the standard innoculum to a variety of concentrations

of phenol in sterile distilled water the

concentration bi.11 1 Abeitwoen 1/95 and 1/120.

Al iquots of the mixture of pheool and ancter ia were

removed at intervals of 2.5, 5, 7.5 and 10 minutes,

463,533

4,2 160 n2 nutrient broths were innoculated with each of the

aliquots and the presence or absence of bacterial

growth in the broth was noted after 24 and 48 hours.

From this test it was establishod that Pseudomonas

aeruginosa survived for 5 minutes in phenol of

concentration 1/105 whereas the other three were

completely killed. The same test was conducted

using cetyltrimethyl ammonium bromide "Cetrimide"

at concentrations between 0.01f; and 5% in sterile

distilled water. It was established likewise that

Pseudomonas aeruginosa was the most resistant of

the four organisms to the action of cetyltrimethyl

ammonium bromide "Cetrimide" and that it would survive

for 5 minutes at a concentration of 0.01% of the

"Cetrimide".

A concentration containing 1% of the

fluorochemical surfactant FCS1 was prepared with

sterile distilled water and added to both the phenol 1/105 and "Cetrimide" 0.01% so that there were equal

quantities of fluorochemical surfactant and the

bactericides present. It was observed that

Pseudomonas aeruginosa no longer.survived for

minutes in the solutions containing the

fluorochemical. It was similarly observed that the

other three organisms survived for shorter times-in

bactericidal solutions containing the fluorochemical

than in corresponding concentrations of either phenol

or "Cetrimide alone.

46 533

42 160n2 Example 2

Solutions of fluorochemical surfactants FCS 1-5 were prepared in sterile distilled'water and added to a 1% phenol solution to provide final

concentrations of fluorochemical surfactant of

0.05%, 0.025%, 0.0125% and 0.00625% in

each test solution. 0.2 ml of Pseudomonas

aeruginosa culture was added to 5 ml of each test

solution. A small quantity was removed from each

tube after 5 minutes and used to innoculate a

nutrient broth. The broths were examined after

24 hours and 48 hours to ascertain whether or not

bacteria had been able to grow.

It was observed that in all concentrations

the five surfactants improved the rate of kill of

the phenol. The higher concentrations of

surfactant in phenol killed all bacteria after

minutes and the lower concentration reduced the

numbers of active organisms capable of subsequent

growth in the broth to a greater degree then phenol alone was able to do. Example 3

Test solutions were prepared conltaining 0.8%

phenol and 0.0125% of one of the fluorochemical

surfactants FCS 1, 5 or 6. To 5 nl of each of these

test solutions, 0.2 ml of Pseudomonas aeruginosa

standard innoculation as used in Examples 1 and 2

463.533

42 1.6 0 [72 at was added. 0.2 ml of thie mixtuwv was romoved addition of 1-minute intervals, diluted by the a 1.j8 pm1 of sterile saline -solut ion and finally solution was tenfold dilution-in sterile saline presenit. made in order to observe the ornanisms Pseudomnas The number of viable organisms of final diluted aeruginosa present in each ml.of innoculating a solution was then estimated by of an agar plate. measured volume onto the surface 0 C for 24 hours and The plates were incubated at 37 produced after incubation the number of colonies count are shown was counted. The results of the in Table 1. Table 1I

per ml of Solution Compnent Number of Viable, Organisms min 2min 3min 4min

xO 3510 x1 8 x107 3 2 6 .7x1 4 7x10 2.x0 <.5x10 Phenol fCS5 .34x10 8

5 3 2 Phenol+FCS6 1.2x10 <1.5x10 <30.5X10

could be counted The lowest number of orolanisms which was l.5X102 in this test.

The bactericidal action of 1,6-di(.4-chloropheny3L (commonly called diouanido) hexane diqlucoflate

4 63. 533

"chlorolhexidine") is 4.2 160 n2 very fast compared with many other bactericides but it is shown in this example that the bactericidal action is accelerated by the

addition of the fluorochemical surfactants 1 and 7. The bacterium selected for test was a gram

negative bacterium Escherichia coli. Concentrations

of "chlorohexidine" in water were prepared at

and 100 ug per mol and the bactericidal effect

measured by expressing the ratio of the number of

the bacteria killed to the number surviving after

various stated time periods. The ratio is quoted as logarithmic units to base 10 "log kill". The same measurements of bacteria killed after the

same time periods were made.for solutions of

"chlorohexidine" and either surfactant FCS1 or 7 similar concentrations. The results are prosented in Table 2 and it may be noted that very marked

increases in "log kill".were obtained when the

fluorocarbon surfactants were added to 25 and

jig per ml concentrations of "chlorohexidine". At

the concentration of 100 ug per ml the increase

observed was less significant.

463.533

42 160n2 Table 2

k"il' MtC'r j imo' p'riodI

Coii'poIl"fL 10 30 A so oO S'c 12( stcl

0.2 0.2 1.7 2.2 Chlorohxidifl 25

I Chiorohexidinel 25) 0.7 1 1.7 2.2 2.9 FCS1 i

1025) 0 .7 1.7 2 .2 2.6 C I d FCS7

1.2 2.2 3.2 3.8 Chlorohexidine: 25) FCS1 100)

25) 1.2 2.7 4.1 5.9 Chlorohexidine FCS7 100)

1.7 2.2 3.2 3.6 Chlorohexidine 50

.1.9 2.7 3.5 4.2 Chlorohexidine! 501 FCS1 50) 2.8 4.1 4.5 5.9 Chlorohexidine 1 +FCS7

~chiorobexidine 100 2.5

SChlorohexidine I FCS1 100) 100) 2.5 4.2 4.6 5.9

46a533

4 .2 160z Example

The tests described in Example 3 were repeated

usino a 0.4' solution of phenol and 0.0125% of the

fluorochemical surfactants 4 and 6. The results

are shown in Table 3.

Table 3

Example 6

The tests described in Example 3 were repeated

using the fluorochemical surfactants 1 and 6 in

solutions of cetyl dimethyl ammonium chloride (CDAC)

in water. The results are as shown in Table 4.

463.533

421~6 0 nl2

Nuinber Lif Viahle( )nnisn po, mlj of ao 1 Component1mm I2Ti j 4m

8 8 5.7x10 3.,xlO kwater 8 4 l.45:x10 1 2.25x10 -O Water 4 4 .12xl 2.4xl0 icD)Ac 0.005% 3. 9x:10 1. 35x10 I~d1O~I ),1A 6.15x0'

Example 7

solutions of surfactant were prepared in sterile of distilled water and added to a 0.025% solution

orthophenyl phenol.(OPP) in a 205% dimethyl formamide/

807c water mixture (by volume) to provide a concentration test of 0.0125% fluorochemical surfactant in each solution. 0.2 ml of aram negative Pseudomonas to 5 ml aeroginosa culture was added as the bactericide

463.53

4.2 160 n2 of sterile distilled water and 0.125% of orthophenyl

phenol (for comparative test purposes) and to 5 ml of each of the t'st solutions. A 0.2 ml sample was

removed from each solution after various time

intervals and diluted to 2 ml with sterile saline

solution, and finally diluted tenfold in saline

solution. The number of visible organisms present

in each ml of final diluted solution was estimated

by innoculating ameasured volume on the surface of

an agar plate. The plates were incubated at 37°C

for 24 hours and the number of colonies produced

was counted. The lowest number of organisms which 2 could be counted was 1.5 x 10 in this test. The results of the count are shown in Tables and 6. Table

tNuita of Viable hOranisnsper ml of solution Component s sec' 30 sec 60 sec 90 sec 120 sec

8 5.6x10 Water 1.2x10 9 7 OPP 1.3x10 5.1x10

3 10 3 OPP FCS6 3.0x10 3 6.2x10 9.6x 9.0x102 2.Ox104 3 OPP FCS3 1.lx107 1.3x104 5.3x10 1.5x10 2.0x10

OPP FCS8 4.5x10 2 1.5x10 3 2.5x10 3 1.7x10 3 <1.5x10 2

4.2 16 0n2 Table 6

Nunbcxr of k'ikblc' Ornan i, srn~ (If Solution1 Components seod 30 sec! 60 S C 90 sOc~ 120 sec

9 Water 2 .7xl0 2.3x0 9 6 9 OPP C73.lxlO l.x0151 2.5x10

6 6 OP+FC 1 .8x1 11.8x106 .x 1.1 6.6xlO

6 OPP.+ FCS9' 22x10 '6.6x10 6.OxlO :<L5xl <l510

OPP FCS1O 3.9x10 1 1.lxl065 l.lXlO 5i16.OxlO 4 9.2x10 3

Example 8

The' tests described in Example 7 werv repeated

using a 0.025% solution of orthophvnyl orthochioro-

phenol (OCOCP) and 0.125% of the fluorochemical,

surfactants 1 to 6. The results are shown in

Tables 7 and 8.

Table 7

Numbter cd Viable Organisms per m of Solution Component sec 30 sec 60 sec 90 sec 120 sec

9 9 Water 2.7x10 .4x10

8 6 6 OPOCP l.6x10 7.4x10 6.6xl10 8.3x1O 65.9x1C)6

3 3 3 2 2 2 OFP CS 8X106 8.4x10 2.4x10 1.5x10 7.5x10 3 3 7.lxl03!3.9xl02 9.0X10 4.2x10 2.1x10 4 441 4 33 444 OPOCP+FCS8 6.0x10 'l.1x10 7.2x10 l.1x10 l.2x10

42 60 Tabie 8 fl2

I of V; ahie0:l;"'~jrri OI l

Component sec' 30 sec: sec: 90 seci 120 Sc

1 9 Water 2.7x10 2.3x10 8 7 OPOCP 16x10 1.0x10 51 5' 5 66 6 OPOCP+FCS7 6.8xlo 8.0x10 6.2x10 2.0x10 1 1.5x10

OFOCP+FCS9 1.5xlO<.xO<.x1415l <.x 7 3.6xlO3 4.2x10I3!3.9x10 31 3.5x10 03 OPOCP+FCS1O 5.7x10O

Example 9

The tests described in Example 7 were repeated

using a 0.025% solution of 4-chloro-3,5-xylenol (CX)

in 2.5% dimethylformamide/97.5% water mixture (by

volume) and 0.0125% of fluorocarbon surfactant 1.

The results are shown in Table 9.

Table 9

Number of ViableOrganisns perml of Sdution

sec! 30 se 60 se 90 sec 120 sec

IWater 3.0xl0 2 5x109

Water+!XMF 1. 13Xn

8 8 CX 1.3xl0 1. 2X10 8.6x1O 3.0x10 2.6 X10 2 CX+FCS6 l.3x106 i 2.lxlO 2. 55.xlO1 1. 5x10 2 i. 5x10

42160 2 Example 10

The tests described in Example 7 were repeated

usino a 0.0255 solution of orthophenyl phenol (OPP) 7 (by in 2.5% dimethylformcamidc/9 water mixturt

volume) and 0.0125%, of fluorochji cal. sur factan ts.

The results are shown in Tables 10 and 11.

Table

Number of Viable Organisms per ml of Solution Component 1 e sec'30 sec! 60 secl 90 sec; 120 sec

9 9 Water 1.3x10 3.5x10

9 9 9 9 9 OPP 1.510 1.5x10 1.4xl0 l.0x10 3.5x10 3 2 PP+FCS7 4.Ox033.8x10 3.X10 1.5x10 1<1.5x10

Table 11

Number 'of Viable Organins per ml of Solution ComponentI sec 30 sec! 60 sec, 90 sec 120 sec

9 9 Water 1.3x10 3.5x10 9 OPP l.5x10 1.501.4x 1.0x10 3.5x10 3+ 33 2 02 !<1.5x,02 OPP+FCS9, 4.0x10O 1.0x10 1.5x10 1.5x10 11

The fluorochemical surfactant composition

contained the fluorochemicals rCS9, 10 and 11 in the

molar ratios 1:5:1.

463,533

4.2 160 /?2 Examplde 11

Solutions containing the fluorochemical

surfactants IFCS9. 10 and 11 (in -ho molar ratio

1:5:1) were prepared in sterile dliqtilled water

and added to the following solutions of

orthophenyl nonochiorophenol (OPNICP a mixture

of orthophenyl orthochiorophenol a~nd orthophenyl parachiorophenol):

0.035r OPMCP in 3%c dimethylformamidt-/97% water (v/v)

0.01517 OPMCP in 1.5% dimethylformamidc'/971 water (v/v)

0.2 ml of Staphylococcus aureus culture was

added as the tocAy ofda of tets

solutions and to Izal Pine 4 f(diluted to 1/100),

0.06%1 OPMCP (in 6% dimethylfarmamide/94% water),

0.03%.OPMCP and 0.015% OPMCP without fluorochemical

surfactants for comparative purposes.

The tests were then carried out as d escribed

in Example 7. The results art! shown in Table.12.

463.53 3

4.2 160n2 Table 12

Numiber of mi.b'jiL-~-prul Solut ion Component I 1 soc; 30 sec 00 sec 120 sec L. 'Ia Pine' 5 3 3 nzIzal Pine? 1.0x10 1. 2 7x105j7. 5x10 5. 8x10 4. 3x10 31 51 4 3 310 2 0. O% OPMCP 1.5x10 i4.5x1I( 8.8X1 5.7 9x10

0.03-, OPMCP 2.4x06i 7.2xlO 4 S4 !1214 1.2x4 6. 4x10 3 3. x10 3

0.03% OPMCP 2 0.000551 FCS9, 10, 2x104 1.ax106;7. 3.8x10O 7. 5x0 11

6 5 4 0.015% OPMCP 1.2x10 2.lxl0 13.6x10 1.4x105

0.0158% OPMCP 6 5 8.4x10 4 0.000825%o FCS9, 10 1.1xlO ;1.5:xO 8.xl 1. 6xlO 11

This example shows that the bactericidal effect

of 'Zal Pine' or 0.06% OPMCP can be achieved at 100 reduced levels of phenolic compound content (0.03%,

0.015%) by the addition of a very small quantity of

fluorochemical surfactants. 'Zal Pine' is a trademark

of a disinfectant manufactured by Newton Chambers.

463,533

Claims (1)

1. 42160nz2 The claims defining the invention are as follows:-

   1. A method of improving the activity of an

   antibacterial compound w'hich addiing

   to the antibacterial compound a surface-active

   agent containing a terminal aliphatic

   perfluorocarbon group of at least three carbon

   atoms and a hydrophilic group.

   2. A method of improving the activity of

   antibacterial compounds substantially as

   described with reference to the Examples.

   3. An antibacterial composition comprising a

   compound having antibacterial ativity and a

   surface-active agent containing a terminall

   perfluorocarbon group of at least three carbon

   atoms and a hydrophilic group.

   4. A composition as claimed in Claim 3 wherein

   the antibacterial compound is a phenolic

   compound.

   A composition as claimed in Claim 4 wherein

   the phenolic compound is phenol.

   6. A composition as claimed in Claim 4 wherein

   the phenolic compound is a chlorophenol.

   7. A composition as claimed in Claim 6 wherein

   the chlorophcnol is a phenyl chlorophenol. 8. A composition as claimed in Claim 7 wherein

   the phenyl chlorophenol is orthophenyl

   orthochlorophtnol.

   5 463.533

   42 1 l 60i1 n2 C I im wl -r'i 0. A ciompos i t ion as i;li

   the chloropl l'no1 is a chloi-,xyl -I)I l.

   A conposition as claime'd in (Clai, wherefin

   the chloroxylcnol is 4-chloro-3,5-xylonol.

   11. A composition as claimed in Claim 4 wherein

   the phenolic compound is a phenyl phenol.

   12. A composition as claimed in Claim 11 wherein

   the phenyl phenol is orthophenyl phenol.

   13. A composition as claimed in Claim 4 wherein

   the phenolic compound is a cresol.

   14. A composition as claimed in Claim 3 wherein

   the antibacterial compound is an alkyl ammonium

   compound. A composition as claimed in Claim 14 wherein

   the alkyl ammonium compound is a cetyl methyl

   ammonium halide.

   16 A composition as claimed in Claim 15 wherein

   the cetyl methyl ammonium halide is cetyl

   trimethyl ammonium bromide.

   17. A composition as claimed in Claim 15 wherein

   the cetyl methyl ammonium halide is cetyl

   dimethyl ammonium chloride.

   18. A composition as claimed in Claim 3 wherein

   the antibacterial compound is a 1,6-di(phenyl

   diguanido) hexane or a salt thereof.

   463.533

   19. 4.2 160 n2 A composition as claimed in Claim 18 wherein the diguanido hIIxan>, compound i.s 1 ,o-di(4-chloro-

   phleny.l di !uaido) hexane o. a salt tlehreof.

   A composition as claimed in any one of

   Claims 3 to 19 wherein the perfluorocarbon

   group of the surface-active agent is a

   straight or branched group having a terminal

   chain portion of at least three carbon atoms.

   21. A composition as claimed in Claim 20 wherein

   the perfluorocarbon group of the surface-active

   agent is a branched group derived from an

   oligomer of tetrafluoroethylene (C F 2 4 n wherein n is 4, 5 or 6. 22. A composition as claimed in any one of Claims 3 to 21 wherein the hydrophilic group is

   an anionic group. 23. A composition as claimed in Claim 22 wherein

   the anionic group is carboxylate, phosphate,

   phosphonate or sulphonate. 24. A composition as claimed in any one of

   Claims 3 to 21 wherein the hydrophilic group.

   is a non-ionic group. A composition as claimed in Claim 24 wherein

   the non-ionic group is an oxyalkylene chain

   containing an oxygen/carbon ratio greater than 0.3.

   463.533

   4.2 16 0 n2 26. A composition as claimed in any one of Claims 3 to 21 wherein the hydrophilic group is a cationic group.

   27. A composition as claimed in Claim 2o wherein

   the cationic group is a quaternary nitronen group.

   28. A composition as claimed in Claim 27 wherein

   the quaternary nitrogen group is an alkyl

   ammonium group.

   29. A composition as claimed in Claim 27 wherein

   the quaternary nitrogen group is a pyridinium

   group.

   A composition as claimed in any one of Claims 3 to 23 wherein the surface-active

   agent is a compound selected from the group consisting of RfOC H4SO03-

   wherein Rf is C10F19 M is alkali-metal or ammonium

   31. A composition as claimed in any one of Claims 3 to 20 and Claims 26 to 28 wherein the

   surface-active agent is a compound selected

   from the group consisting of

   R SO2 NIl(CII 2 3R 3 A"

   wherein PR is C F17

   each R is Cll or C 115

   A is Cl, Br, I or CII SO 4

   463.533

   4,2 160 n2 32. 'A composition as claimed in any one of

   Claims 3 to 21 and Claims 26 to 28 wherein

   the surface-active agent is a compound

   selected from the group consisting of

   RfOC 6 4 SO 2 NH(C11 2 3R 3 A-

   wherein Rf is C8F15 C10F19 or C12F23 each R is CH 3 or C2H

   A is Cl, Br, I or CH3SO4

   33. A composition as claimed in any one of

   Claims 3 to 21 and Claims 26 to 28 wherein

   the surface-active agent is a compound

   selected from the group consisting of

   R OC6H4CH24R 3 A-

   wherein Rf is C8 F15 C 10F 19 or C 1 2F23

   each R is CH or C2H

   A is Cl, Br, I or CH 2 SO

   34. A composition as claimed in any one of

   Claims 3 to 21 and Claims 26, 27 or 29 wherein

   the surface-active agent is a compound selected

   from the group consisting of

   RfOC 6H 4 CH 2 (NC5 5 A-

   wherein Rf is. CF15 C 1 0 F19 or C1 2F23 A is Cl, Br, I or CHISO,

   1

   4 .2160 any one of A composition as claimed in 27 or 29 wherein Claims 3 to 21 and Claims 26, a compound selected the surface-active agent is from the croup consisting of

   RfO(C 5 H4 i1)R A- wherein Rf is C8F15' C1oFI9 or C 12F23

   R is CH 3 or C21t

   A is Cl, Br, I or CH 3 S04

   one of 36. A composition as claimed in any of Claims 3 to 35 wherein the proportion is in the fluorocarbon surface-active agent weight per range from 0.001 to 10 parts by compound. 1 part by weight of antibacterial Claim 36 wherein 37. A composition as claimed in surface-active the proportion of fluorocarbon 0.01 to 5 parts by agent is in the range from of antibacterial weight per 1 part by weight compound. Claim 37 wherein 38. A composition as claimed in surface-active the proportion of fluorocarbon 0.1 to 2.0 parts agent is in the range from of antibacterial by weight per 1 part by weight compound. in claim 3 and 39. A composition as claimed with reference to substantially as described the Examples. DATED: 8th llay, 1972 T PHIL IP3S .IUODE AND FIT ZPATRICK Att orne~3 for L 2A- -1TF-,I,3 IDUITRIE LI!ITED P.B. TUNNICLIFFE AGENT FOR THE APPLICANTS

   463.533