Anti-microbial compositions comprising an aqueous solution of a germicidal polymeric nitrogen compound and a potentiating oxidizing agent

An anti-microbial composition comprises an aqueous solution of a germicidal polymeric nitrogen compound and an oxidizing agent which potentiates the activity of the compound. The polymeric nitrogen compound includes a germicidal quaternary ammonium compound or a polyguanide compound. The oxidizing agent has a standard reduction potential between 0.85 and 2.0 volts, is soluble in water, non-toxic and enhances the activity germicidal of the nitrogen polymer at low concentrations. Suitable oxidizing agents include halogen oxides, oxyhalogens, halogens, and inorganic and organic peroxides.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This application relates to anti-microbial compositions, and, more 
particularly, to improved disinfectant compositions for treatment of 
contact lenses and industrial materials. 
2. Description of the Prior Art 
Various compositions and methods are known for use in sterilization and 
cleaning of contact lenses, such as soft contact lenses, and for 
sanitization of industrial materials, such as water treatment systems. 
However, it is desired to provide new and improved anti-microbial 
compositions and methods of use which show an enhanced anti-microbial 
activity at low concentrations. 
As stated by R. E. Phares in U.S. Pat. No. 3,689,673, sterilization of 
hydrophilic soft contact lenses may be carried out by soaking in an 
aqueous solution containing approximately 0.001-0.01% chlorhexidine for a 
time sufficient to sterilize the lens. 
Various related methods are disclosed in other U.S. patents. U.S. Pat. No. 
3,591,329 discloses the use of a cationic resin exchange material 
impregnated with active metallic silver. U.S. Pat. No. 3,755,561 teaches 
using an aqueous solution of polyvinyl pyrrolidone, a polyalkylene glycol 
and thimerosal. U.S. Pat. No. 3,873,696 discloses using a combination of 
potassium peroxymonosulfate in the presence of sodium chloride. In U.S. 
Pat. No. 3,876,768 is described the use of a chlorinated trisodium 
phosphate material which is similar to hypochlorite. U.S. Pat. No. 
3,888,782 relates to the using of chlorhexidine and polyvinyl pyrrolidone. 
The use of an iodoform solution containing iodine, polyvinyl alcohol and 
boric acid is disclosed in U.S. Pat. No. 3,911,107. U.S. Pat. No. 
3,912,450 proposes using a combination of an alcoholic glutaraldehyde 
solution containing a surfactant in conjunction with an ultrasonic 
radiation device. 
U.S. Pat. No. 3,888,782 more particularly discloses an aqueous, 
substantially isotonic cleaning and sterilizing solution for plastic 
hydrophilic soft contact lenses containing, as active ingredients, 
chlorhexidine and polyvinylpyrrolidone. The solution is said to be 
non-toxic to the eye of the wearer of soft contact lenses and in the 
presence of a suitable amount of water soluble 
polyhydroxyethylmethacrylate to prevent the build-up of opaque deposits on 
the surfaces of soft contact lenses. 
U.S. Pat. No. 4,029,817 discloses that soft contact lenses may be 
sterilized by contacting soft lenses with a sterile, aqueous, 
substantially isotonic solution containing as an active ingredient, an 
effective amount of a quaternary ammonium compound having the structural 
formula: 
##STR1## 
wherein R represents saturated or unsaturated alkyl residues of fatty 
acids and mixtures thereof containing from about 12-18 carbon atoms and 
preferably tallow, A is a non-toxic anion and R.sub.1, R.sub.2, and 
R.sub.3 are the same or different and represent alkyl radicals having 1-3 
carbon atoms; and together with a detoxifying amount of a non-toxic 
compound selected from the group consisting of water soluble 
polyhydroxyethyl methacrylate, carboxymethylcellulose, polyoxyethylene 
sorbitan fatty acids esters, polyoxyethylene alcohols, 
polyvinylpyrrolidone and mixtures thereof. 
Many known quaternary ammonium compounds are generally good bactericides 
but are also irritating such as, for example, when they come into contact 
with the eye. Some of these compounds are moreover cationic and can be 
absorbed by porous surfaces and are difficult to remove. Where these 
compounds have been made less absorbent, they have never achieved the 
degree of perfection which would enable their use in critical applications 
such as with soft contact lenses. 
Stabilized chlorine dioxide is known to be a powerful broad spectrum 
anti-microbial agent, effective in killing gram-positive and gram-negative 
bacteria, viruses, fungi, etc. The true composition of stabilized chlorine 
dioxide is an addition compound with the approximate formula of 2Na.sub.2 
CO.sub.3.3H.sub.2 O.sub.2.ClO.sub.2. Stabilized chlorine dioxide has long 
been known as a much more effective anti-microbial agent than chlorine or 
hypochlorite. It completely consumes bacteria and other micro-organisms 
thereby preventing the formation of resistant strains. Although stabilized 
chlorine dioxide is a powerful oxidizing agent, its oxidation potential is 
less than that of hydrogen peroxide and it does not chlorinate organic 
compounds. It is purported to have 2.6 times the germicidal power of 
chlorine, yet it is 10 times as stable in aqueous solution. Stabilized 
chlorine dioxide is commercially available for a variety of industrial 
uses. However, it has never been used as an anti-microbial agent for soft 
contact lenses. 
A 5% solution of stabilized chlorine dioxide is colorless, non-corrosive 
and easy to handle. It can be diluted to any concentration with water. It 
has government approval for many uses throughout the world. The product is 
inexpensive and has a long shelf life. The efficacy of stabilized chlorine 
dioxide increases as the pH value approaches the acid side. It does not 
have a characteristic chlorine-type odor. Stabilized chlorine dioxide has 
the unique property of oxygenation without chlorination. It destroys 
micro-organisms by reaction with cell structure and by speeding up the 
metabolism to the detriment of cell growth. It prevents immunity build-up. 
As it is infinitely soluble in water, any occluded chlorine dioxide that 
would occur within a soft lens could be readily removed by amply washing 
with distilled water or an isotonic solution. The oxidation potential for 
chlorine dioxide is ClO.sub.2 +4H.sup.+ +5e.sup.- =Cl.sup.- +2H.sub.2 O 
1.50 volts. The oxidation potential for hydrogen peroxide is H.sub.2 
O.sub.2 +2H.sup.+ +2e.sup.- =2H.sub.2 O 1.77 volts. 
Generally, U.S. Pat. No. 4,073,888 teaches the provision of a cold 
sterilization product for use on hard surfaces in hospitals, and kitchens, 
for medical instruments, and so forth. At the concentrations described, it 
is not, however, contemplated for use in disinfecting soft contact lenses, 
because (1) it would be irritating to the eye and (2) absorption of the 
quaternary salt in soft lenses would be a major problem. 
More specifically, U.S. Pat. No. 4,073,888 relates to a composition of 
matter which is especially adapted for hard surface, cold sanitization and 
sterilization especially for killing spores and, more particularly, to 
aqueous compositions of matter containing chlorine dioxide and certain 
selected quaternary ammonium salts having the formula 
##STR2## 
wherein R' and R" are alkyl radicals whose total carbon atoms number from 
18 to 24, and preferably from 20-22. It is preferred that R' and R" be 
identical (symmetrical) but this is not necessary although each of the R' 
and R" radicals should have at least 8 carbon atoms. X is a chlorine, 
bromine, or any non-toxic non-interfering anion such as is known for the 
quaternary ammonium salts. 
In order to prepare the composition of U.S. Pat. No. 4,073,888, the 
chlorine dioxide may be used either in pure form as well as a stabilized 
chlorine dioxide complex and in solution or suspension either aqueous or 
non-aqueous in concentrations of from 0.1% to 6.0%. It has been found, 
according to U.S. Pat. No. 4,073,888, generally necessary to employ one or 
more emulsifiers for the disclosed compositions. Those emulsifiers are 
generally linear compounds which are primary alcohol ethoxylates having 12 
moles of ethylene oxide and the primary alcohol portion being derived 
from C.sub.12 -C.sub.15. The optimum range for use in this composition is 
that the primary alcohol contains from 5 to 12 moles of ethylene oxide, 
but from 3 to 15 moles are useful. It is believed that the sporicidal 
activity of these compounds is enhanced by the use of alcohol which of 
course is not permissible for use in the cleaning of soft contact lenses. 
U.S. Pat. No. 4,026,945 discloses synthetic anti-microbial quaternary 
ammonium copolymers. The copolymers are prepared by the condensation of at 
least two difunctional tertiary amines using a molar quantity of 
1,4-dihalo-2-butene equal to the molar sum of the difunctional tertiary 
amines in the mixture. The product is disclosed as effective for the 
anti-microbial treatment of water but is not good for critical 
applications such as soft contact lenses as mentioned above. 
One of the features of the copolymers of U.S. Pat. No. 4,026,945 is that 
the quaternary ammonium moieties are part of the long polymeric chain 
rather than being quaternary ammonium moieties on branches that are bonded 
to the polymeric chain. Another feature is that the copolymer is a unique 
reaction product and not a mere mechanical mixture of separate polymers. 
Therefore, the copolymers cannot be separated into constituent components, 
as would be the case if they were mere mechanical mixtures. 
Another feature of U.S. Pat. No. 4,026,945 is that the primary chemical 
units comprising the polymeric chain are not identically repetitive as 
they would be if the product were an ordinary polymer. On the contrary, 
the several primary chemical units of the copolymer are randomly 
distributed in the polymeric chain. 
U.S. Pat. No. 3,428,576 describes polymeric diguanides and their salts 
which have been found to be effective anti-microbial agents. These 
compounds are characterized by the recurring unit 
##STR3## 
where R is a divalent radical, preferably an aliphatic hydrocarbon chain 
of 4 to 12 carbon atoms, and n is a number such that the molecular weight 
of the polydiguanide is at least about 800 and upwards to about 1200, and 
higher, and preferably from about 1,000 to about 5,000. Salts of these 
amino/imino polymeric compounds may be made with acids such as 
hydrochloric acid, sulfuric acid, acetic acid, gluconic acid, etc. A 
preferred product is the hydrochloric acid salt of poly(hexamethylene 
diguanide). The product is commercially available from ICI Americas Inc. 
under the trade name IL-779. This product is an excellent anti-microbial 
agent, even in the presence of organic matter. It has a low order of 
toxicity and is chemically stable, non-corrosive, and odor-free. It is 
effective in concentrations as low as 0.001%. 
In accordance with the above-described products, the required 
characteristics for an effective product are contained in 
positively-charged, nitrogen-containing cationic polymers, such as the 
quaternary ammonium compounds described in U.S. Pat. Nos. 4,026,945 and 
4,027,020 and the amino and/or imino compounds and their salts, for 
example, the polydiguanides described in U.S. Pat. No. 3,428,576 as well 
as U.S. Pat. No. 2,643,232. These types of compounds having a plurality of 
cationic nitrogen species result in a more potent anti-microbial action, 
probably because of more points of interaction with the microbial cell 
wall. The other important factor is the higher molecular weight. The 
larger polymeric molecules are not as readily absorbed into the 
hydrophilic lens material as are the small monomeric molecules. For 
industrial applications, however, the molecular weight of the polymer is 
less significant. 
Other oxidizing agents have been useful as disinfectants for industrial 
applications. For example, hydrogen peroxide is widely used as an 
antiseptic. It owes its action to its ready release of nascent oxygen with 
by product formation of water, but the effect is of short duration. 
Contrary to common belief, hydrogen peroxide is not decomposed instantly 
under usual conditions in acid solution unless its decomposition is 
catalyzed. Solutions of hydrogen peroxide also have poor power of 
penetration and are comparatively weak antiseptics. Therefore, there is an 
obvious need for expanding its biocidal spectrum and enhancing its 
duration of activity. 
Hydrogen peroxide has been used also as a disinfectant for soft contact 
lenses; however in a 3.0 wt. percent solution only. In practice such 
solutions require the additional step of decomposing residual peroxide 
since any non-decomposed peroxide causes considerable damage to the easily 
oxidizable hydrophilic lenses polymer resulting in discoloration and 
changes in the visual acuity of the lenses. 
In this invention, anti-microbial compositions containing polymeric 
germicides and peroxides such as hydrogen peroxide permit a surprisingly 
large reduction in the amount of the peroxide constituent while 
substantially increasing the activity of the composition. This provides a 
completely unexpected improvement in effectiveness-to-concentration 
characteristics of the compositions. For example, when combined with 
germicidal polymeric nitrogen compounds of the type described herein, 
peroxides can be used in such relatively low concentrations that the 
irritant effect of the peroxide is avoided. 
SUMMARY OF THE INVENTION 
What is provided herein are anti-microbial compositions comprising an 
aqueous solution of a germicidal polymeric nitrogen compound and an 
oxidizing agent which potentiates the activity of said compound at low 
concentrations. The oxidizing agent has a standard reduction potential of 
at least 0.85 volts but less than 2.0 volts, in which range it can oxidize 
the polymeric nitrogen compound at low concentrations in situ to form an 
oxidized nitrogen compound which possesses enhanced germicidal activity. 
The oxidizing agent used herein is soluble in water, non-toxic and, for 
use in contact lenses sterilization solutions, non-irritating to ocular 
tissue. 
Suitable oxidizing agents which potentiate the activity of germicidal 
polymeric nitrogen compounds include halogenoxides, oxyhalogen acids and 
salts, halogens, halogen halides, inorganic and water soluble organic 
peroxides and permanganates, including chlorine dioxide, hypochlorites, 
chlorites, chlorates, perchlorates, hypobromites, bromates, chlorine, 
bromine, bromine chloride, hydrogen peroxide, persulfates, perborates, 
peracetic acid, t-butylhydroperoxide, percarbonates, peroxy acids and 
salts of molybdenum, tungsten and chromium and permanganates. Such 
oxidizing agents have the requisite characteristics for use herein, 
particularly (1) a standard reduction potential in the range of 0.85 and 
2.0 volts, (2) solubility in water, and (3) non-toxic and non-irritating 
at low concentrations. 
The polymeric germicide may be, for example, a quaternary ammonium compound 
or an amino and/or imino compound or salts thereof, and preferably one the 
size and shape of which is adapted to prevent the absorption thereof by 
porous surfaces such as characterizes the materials from which soft 
contact lenses are made. These components are used in solution in water. 
In one preferred embodiment of the invention, the aforesaid quaternary 
ammonium compound is a copolymer of at least one difunctional tertiary 
amine and a dihalo organic compound such as, for example, 
1,4-dihalo-2-butene. Monofunctional tertiary amines are also useful. 
Polydiguanides are an example of amino/imino compounds which can also be 
used in accordance with preferred embodiments of the invention. 
The anti-microbial compositions of the present invention, when used as 
disinfectants for soft contact lenses, generally comprise about 0.001 to 
0.05 weight percent of the germicidal polymer and 0.001 to 0.05 weight 
percent of the oxidizing agent. For industrial applications, such as 
biocidal treatment of water or sterilization of hospital rooms, the 
compositions are generally about 0.001 to 5.0 weight percent of each. 
The pH of the composition generally is about 6.5 to 7.5 when used as a soft 
lens disinfectant, and about 5.5 to 8.5 for industrial applications. 
DETAILED DESCRIPTION OF THE INVENTION 
Table I below is a list of suitable oxidizing agents for use in the 
compositions of the invention. These oxidizing agents are water soluble, 
non-toxic, non-irritating and have a standard reduction potential of 
greater than 0.85 volts but less than 2.0 volts which potentiates the 
germicidal properties of the polymeric nitrogen compound. 
TABLE I 
______________________________________ 
Halogen Oxides 
ClO.sub.2 + 4H.sup.+ + 5e.sup.- = Cl.sup.- + 2H.sub.2 O 
1.50 v 
Oxyhalogens 
HClO + H.sub.2 O + 2e.sup.- = Cl.sup.- + H.sub.2 O 
1.49 v 
HClO.sub.2 + 3H.sup.+ + 3e.sup.- = 1/2Cl.sub.2 + 2H.sub.2 O 
1.63 v 
ClO.sub.3.sup.- + 2H.sup.+ + e.sup.- = ClO.sub.2 + H.sub.2 
1.15 v 
ClO.sub.4.sup.- + 8H.sup.+ + 8e.sup.- = Cl.sup.- + 3H.sub.2 O 
1.45 v 
HBrO + H.sup.+ + e.sup.- = 1/2Br.sub.2 + H.sub.2 O 
1.59 v 
HIO + H.sup.+ + 2e.sup.- = I.sup.- + H.sub.2 O 
0.99 v 
ClO.sup.- + H.sub.2 O + 2e.sup.- = Cl.sup.- + 2OH.sup.- 
0.90 v 
IO.sub.3.sup.- + 6H.sup.+ + 6e.sup.- = I.sup.- + 3H.sub.2 O 
1.09 v 
ClO.sub.4.sup.- + 8H.sup.+ + 8e.sup.- = Cl.sup.- + 4H.sub.2 O 
1.37 v 
HBrO + H.sup.+ + 2e.sup.- = Br.sup.- + H.sub.2 O 
1.33 v 
BrO.sub.3.sup.- = 6H.sup.+ + 6e.sup.- = Br.sup.- + 3H.sub.2 O 
1.44 v 
Halogens 
Br.sub.2(aq) + 2e.sup.- = 2Br.sup.- 
1.09 v 
Cl.sub.2(aq) + 2e = 2Cl.sup.- 
1.35 v 
Peroxides 
H.sub.2 O.sub.2 + 2H.sup.+ + 2e.sup.- = H.sub.2 O 
1.78 v 
Permanganate 
MnO.sub.4.sup.- + 8H.sup.+ - 8e = Mn.sup.2- + 4H.sub.2 O 
1.49 v 
______________________________________ 
When the oxidizing agents are peroxides they include inorganic and water 
soluble organic peroxides such as have the general formula: 
EQU R--O--O--R.sup.1 
where 
R=hydrogen, alkali or alkaline earth metal; and 
R.sup.1 =hydrogen, alkali or alkaline earth metal, lower alkyl, acetyl, 
benzoyl, etc. 
Peroxides generally have a standard reduction potential about the same as 
hydrogen peroxide (1.78 v) and thus are suitable for potentiating the 
germicidal activities of the polymeric nitrogen compound. While hydrogen 
peroxide is a preferred peroxide for use herein, other peroxides such as 
persulfates, peroxyacetic acids, perborates, percarbonates, lower alkyl 
hydroperoxides, and the peroxyacids or salts of molybdenum, tungsten or 
chromium, may be used as well. 
Suitable germicidal polymeric nitrogen compounds and their preparation for 
use in the compositions of the invention are described below: 
U.S. Pat. No. 4,026,945 discloses co-polymerization products made by 
condensing a mixture of two or more difunctional tertiary amines and a 
molar quantity of 1,4-dichloro-2-butene that is equal to the molar sum of 
the difunctional tertiary amines in the mixture. The difunctional tertiary 
amines are of the type 
##STR4## 
where Z consists of from one to three divalent aliphatic radicals of 2 to 
10 carbon atoms which may contain 0 to 2 double bonds or 0 to 2 hydroxy 
substituents; wherein R' and R" are either the same or different and 
wherein they may be (a) primary or secondary alkyls having 1 to 20 carbon 
atoms, where the sum of the carbon atoms in R' and R" is no greater than 
36, (b) hydroxy or dihydroxy derivatives of the aforesaid primary or 
secondary alkyls, (c) benzyl, (d) alkyl benzyl or (e) combined with N to 
form a heterocyclic group of either 5, 6, or 7 atoms. 
All of the desired characteristics of the compounds of U.S. Pat. No. 
4,026,945 are attained by causing a homogeneous mixture of solution of two 
or more difunctional tertiary amines to react with a molar quantity of 
1,4-dichloro-2-butene which is equal to the molar sum of all of the 
components in the homogeneous mixture of solution of difunctional tertiary 
amines. 
In this manner, if a homogeneous mixture or solution of 
1,4-bis-(dimethylamino)-2-butene having the structure (CH.sub.3).sub.2 
--N--CH.sub.2 --CH=CH--CH.sub.2 --N--(CH.sub.3).sub.2 and N,N'-dimethyl 
piperazine having the structure 
##STR5## 
is reacted with a molar quantity of 1,4-dichloro-2-butene having the 
structure Cl--CH.sub.2 --CH=CH--CH.sub.2 --Cl equal to the molar sum of 
the two difunctional tertiary amines, the two primary units which are part 
of the polymeric chain would be: 
##STR6## 
The ratio of the number of each of these units in the polymeric chain is 
very close to the molar ratio of the two difunctional tertiary amines in 
the starting mixture or solution, but the sequential order in which these 
two units appear in the polymeric chain is completely random, and 
therefore not identically repetitive.

The following examples are some of those given in U.S. Pat. No. 4,026,945. 
EXAMPLE A 
7.1 grams of 1,4-bis-(dimethylamino)-2-butene (0.05 mole) and 5.6 grams of 
diazabicyclo (2.2.2) octane (0.05 mole) are dissolved in 25 grams of 
water, and to the solution are added drop-wise 12.5 grams of 
1,4-dichloro-2-butene (0.01 mole) at such a rate as to keep the 
temperature at about 60.degree. C.-70.degree. C. After addition is 
complete, and the exothermic reaction subsides, the mixture is heated in a 
steam bath for about 1 hour. The resulting solution contains about 50% by 
weight of active copolymer. 
The same procedure can be repeated using as the mixtures of difunctional 
tertiary amines (a) 0.05 mole 1,4-bis-(morpholino)-2-butene and 0.05 mole 
of N,N'-dimethylpiperazine, (b) 0.05 mole of diazabicyclo (2.2.2) octane 
and 0.05 mole of 1,4-di-(N-homopiperidino)-2-butene, (c) 0.05 mole of 
1,4-bis-(dimethylamino)-2-butene and 0.05 mole of N,N,N',N'-tetramethyl 
ethylenediamine. In each synthesis, the weight of water used as a solvent 
is approximately equal to the sum of the weights of the two difunctional 
tertiary amines and 1,4-dichloro-2-butene, so that the final mixture 
contains about 50% by weight of active copolymer. 
EXAMPLE B 
12.8 grams of 1,4-bis-(dimethylamino)-2-butene (0.09 moles) and 1.14 grams 
of N,N'-dimethyl piperazine (0.01 mole) are dissolved in 26 grams of 
water, and to the solution are added drop-wise 12.5 grams of 
1,4-dichloro-2-butene at such a rate as to keep the temperature at about 
60.degree. C.-40.degree. C. After addition is completed, and the 
exothermic reaction subsides, the mixture is heated in a steam bath for 
about 1 hour. The resulting solution contains about 50% weight of active 
copolymer. 
The same procedure can be repeated using as the mixtures of difunctional 
tertiary amines (a) 0.08 mole of 1,4-bis-(dimethylamino)-2-butene and 0.02 
mole of 1,4-bis-(N-morpholino)-2-butene, (b) 0.08 mole of 
1,4-bis-(dimethylamino)-2-butene and 0.02 mole of 
1,4-bis-(N-homopiperidino)-2-butene (c) 0.07 mole of 
1,4-bis-(dimethylamino)-2-butene and 0.03 mole of 1,4-bis-(methyl dodecyl 
amino)-2-butene, and (d) 0.09 mole of 1,4-bis-(dimethylamino)-2-butene, 
and 0.01 mole of 1,4-bis-(methyl dodecylamino)-2-butene. 
In each synthesis, the weight of the water used as a solvent is 
approximately equal to the sum of the weights of the two difunctional 
tertiary amines and 1,4-dichloro-2-butene, so that the final mixture 
contains about 50% by weight of active copolymer. 
U.S. Pat. No. 4,027,020 describes other useful polymeric germicides in the 
form of anti-microbial polymeric quaternary ammonium compounds having 
linear chains which terminate in quaternary ammonium moieties, such 
compounds being formed by polymerization which is carried out in such a 
manner that the linear chains thereof are terminated in random fashion, 
the reaction resulting in the formation of the compounds being a one-step 
reaction between 1,4-dihalo-2-butene and a mixture of a difunctional 
tertiary amine and a monofunctional tertiary amine wherein the molar 
quantity of the difunctional amine is greater than the molar quantity of 
the monofunctional amine. 
The following example from U.S. Pat. No. 4,027,020 exemplifies mono- and 
difunctional tertiary amines: 
EXAMPLE C 
28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) and 1.40 grams of 
triethanolamine (0.01 moles) were dissolved in about 55.5 grams of water 
in a round-bottom flask fitted with a stirrer and reflux condenser, and 
25.63 grams of 1,4-dichloro-2-butene (0.205 moles) were added slowly while 
the mixture was stirred. The reaction mixture was heated to 
60.degree.-70.degree. C. and maintained at that temperature, with 
stirring, for about 6 hours. The reaction was 98% complete, as indicated 
by ionic chloride analysis. The residue contained about 50%, by weight, of 
active material. 
It has now been found that combinations of oxidizing agents such as 
hydrogen peroxide and oxyhalogen compounds, on the one hand, and polymeric 
germicides, on the other hand, permit a surprisingly large reduction in 
the amounts of each of these constituents which must be used. This gives a 
completely unexpected improvement in effectiveness-to-concentration 
characteristics. As a consequence, many new uses for compositions 
containing these two constituents are envisaged. 
For example, to obtain an effective anti-microbial agent based on 
stabilized chlorine dioxide alone, an amount of stabilized chlorine 
dioxide must be employed which would be irritating in ocular applications 
such as the treatment of soft contact lenses. When combined with the 
polymeric compounds mentioned above, such relatively low concentrations of 
stabilized chlorine dioxide may be used that the irritant effect is 
avoided. 
In addition, polymeric compounds have a molecular weight of at least about 
800 and upwards to about 12,000, and higher, and are preferably from about 
1,000 to about 5,000 and have minimal absorbency in soft contact lens 
material. This feature insures that the polymeric compounds are not 
readily absorbed and thus do not tend to concentrate on or in the soft 
contact lenses, or subsequently on or in the ocular tissue, thereby 
further assuring against irritation. This result is moreover further 
amplified by the fact that only a minimal amount of the polymeric compound 
need be used. 
Other polymeric compounds which may be used in accordance with the 
invention are shown by supplier and patent number below. 
Millmaster Onyx Corp. patents referring to polymeric quaternary ammonium 
compounds having germicidal properties: U.S. Pat. Nos. 3,874,870; 
3,923,973; 3,928,323; 3,929,990; 3,931,319; 4,001,432; 4,005,193; 
4,012,446; 4,026,945, 4,027,020; 4,036,959; 4,055,712; 4,091,113. 
ICI Americas Inc. patents referring to polymeric diguanides 
(polydiguanides) having germicidal properties: U.S. Pat. Nos. 2,643,232 
and 3,428,576. Polymeric diguanides are compounds containing amino/imino 
groups and are positively-charged, nitrogen-containing, cationic 
compounds. Some specific compounds which may be used include polymeric 
hexamethylene diguanide and are represented by the formula: 
##STR7## 
These substances can be manufactured by a process which comprises reacting 
a bisdicyanidiamide of the formula 
##STR8## 
with a diamine of the formula 
EQU NH.sub.2 --Y--NH.sub.2 
In one of its simplest forms, the invention merely involves immersing soft 
lenses (poly(2-hydroxyethylmethacrylate, slightly cross-linked) in a 
solution of a combination of Onamer M and stabilized chlorine dioxide. It 
is desirable to make the solution isotonic and for this purpose any of the 
well-known agents may be used. Preferably the pH of the solution is 
adjusted to about 4.5-8.5 and even more preferably to about 7.4 so that 
the lenses will be comfortable when inserted in the eyes. Other materials 
commonly used in contact lens solutions may also be employed such as 
buffering, chelating and thickening agents. 
In order to test the effectiveness of the polymeric germicide, lenses were 
inoculated with various test organisms and then placed in solutions of 
various strengths of Onamer M and stabilized hydrogen peroxide. The 
maximum time to reach sterility for any of the organisms was recorded. The 
test organisms were: Pseudomonas aeruginosa, Staphylococcus aureus, 
Eschericha coli and Candida albicans. 
The following results were obtained. 
______________________________________ 
0.025% by wt. Onamer M 
(U.S. Pat. No. 4,027,020, Ex. 2) 
0.025% by wt. hydrogen peroxide 
30 minutes 
0.009% by wt. Onamer M 
(U.S. Pat. No. 4,027,020) 
0.008% by wt. hydrogen peroxide 
&lt;2 hours 
______________________________________ 
A further example illustrates the effectiveness of combining the 
hydrochloride salt of poly(hexamethylene diguanide) and hydrogen peroxide 
to reduce Aspergillus niger by 3 logs within 6 hours. I1-779 (available 
from ICI Americas Inc. and having a molecular weight of 1100-1300) is a 
twenty percent by weight aqueous solution of this salt. 
______________________________________ 
Disinfecting Solution 
Microorganism 
Control 6 Hours 
______________________________________ 
0.005% polydiguanide 
A. niger 10.sup.8 org/ml 
10.sup.5 orgs/ml 
0.01% hydrogen 
peroxide 
______________________________________ 
All germicides are aqueous solutions and it is simply required to weight 
out of the appropriate percentage by weight needed and dilute with sterile 
water. The solutions can contain 0.7% sodium chloride. 
The following are exemplary concentrated formulations: 
1. 
Onamer M 0.05% by wt. 
Hydrogen peroxide 0.05% by wt. 
Boric acid 2% by wt. 
Adjust to pH 7.0 
Purified water Q.S. to make 100.00% by wt. 
2. 
Polydiguanide 0.05% by wt. 
Sodium peroxide 0.5% by wt. 
Boric acid 2% by wt. 
Adjust to pH 7.0 
Purified water Q.S. to make 100% by wt. 
A solution containing stabilized chlorine dioxide and polydiguanide for use 
in sterilizing contact lenses of all types, including hydrophilic gel 
lenses, may be prepared from the following formulation containing other 
ingredients: 
______________________________________ 
Stabilized chlorine dioxide 
0.005% 
Polydiguanide 0.005% 
Sodium chloride 0.50% 
Boric acid 0.25% 
Trisodium Edetate 0.05% 
Adjust to pH 7.0 
Purified water Q.S. to make 
100.00% 
______________________________________ 
Other oxidizing agents whose half cell reduction potental is at least 0.85 
volts or larger can be utilized provided they meet other safety, ocular 
irritation and stability criteria. Preferred oxidizing agents to be used 
in the invention are stabilized chlorine dioxide, hypochlorite, hydrogen 
peroxide and bromine chloride. The preferred range of these oxidizing 
agents is 0.001%-0.05% by weight in aqueous solution. The preferrable 
range of this polymeric germicide is also 0.001%-0.05% by weight in 
aqueous solution. For industrial applications the oxidizing agent is 
present in an amount up to 5% by weight. 
Other auxiliary components may be included in preparing applicable 
formulations as for example: additional anti-microbial agent, such as 
chlorhexidine, organic mercurials such as thimerosal and phenylmercuric 
acetate; surfactants, such as sodium borate; etc. 
The following additional examples demonstrate the antimicrobial effect of 
solutions of the present invention. All concentrations are by weight in 
aqueous solutions similar to the above examples. 
ADDITIONAL EXAMPLE I 
Using replicate tests a solution containing 0.025% IL-779 and 0.025% sodium 
peroxide, there was obtained a reduction of .gtoreq.99.99% against 
Escherichia coli ATCC #11229 within a 30 minute period. 
A similar result was obtained utilizing 0.025% Onamer M and 0.025% 
peracetic acid. 
ADDITIONAL EXAMPLE II 
The anti-microbial effectiveness of the combination of IL-779, Onamer M and 
hydrogen peroxide was measured by a broth dilution method. The lowest 
concentration of this combination resulting in a complete inhibition of 
visible growth for 48 hours represents the minimum inhibition 
concentration (MIC) value. These values are intended to be used as an 
index of efficacy for preservative applications. 
______________________________________ 
Organism Percent by Weight 
MIC 
______________________________________ 
Bacteria ppm (in which 
both agents are 
present in 
equal amounts) 
Escherichia coli 
0.002% 20 
Pseudomonas aeruginosa 
0.008% 80 
Streptococcus faecolis 
0.001% 10 
Fungi ppm (in which 
both agents are 
present in 
equal amounts) 
Aspergillus niger 
0.04% 400 
Candida albicans 
0.03% 300 
Saccharomyces turbidans 
0.003% 30 
______________________________________ 
This data shows that this combination has broad spectrum activity against a 
wide variety of test organisms. 
ADDITIONAL EXAMPLE III 
This example illustrates the potentiation of antimicrobial activity with 
hydrogen peroxide on both Onamer M and IL-779 against Serratia marcescens, 
Pseudomonas aeruginose, and Candida albicano by D-value determination 
(D-value=time for reduction of inoculum by 90%. 
______________________________________ 
SOLUTION 
Organism Onamer-M Onamer-M IL-779 
______________________________________ 
(10.sup.6 cells) 
(.001 wt %) 
(.001 wt %) 
(.001 wt. %) 
hydrogen Onamer-M 
peroxide (.001 wt %) 
(.001 wt %) 
hydrogen 
peroxide 
(.001 wt %) 
Serratia 4.8 hrs. 1.2 hrs. 30 min. 
marcescens 
ATCC 14041 
Pseudomonas 1 hr. 45 min 15 min 
aeruginosa 
ATCC 9027 
Candida albicans 
&gt;24 hrs &gt;24 hrs. 1.5 hrs. 
ATCC 10231 
______________________________________ 
ADDITIONAL EXAMPLE IV 
This example illustrates the industrial use of the compositions of the 
invention as a recirculating microbiological agent for cooling tower 
treatments against two pure cultures of bacteria. Percent kill of a 
composition of Onamer M and hydrogen peroxide against Aerobacter aerogenes 
and Bacillus subtilis ver. mycoides at pH7. 
______________________________________ 
CONCENTRATION (ppm of each component) 
TIME(Hrs) 5 10 25 50 
______________________________________ 
1 99.0 99.9 100.0 
100.0 
2 100.0 100.0 100.0 
100.0 
3 100.0 100.0 100.0 
100.0 
Bacillus subtilis ver. mycoides 
1 98.0 99.0 100.0 
100.0 
______________________________________ 
Two pure cultures of Algae Percent kill of Onamer M/polyhexamethylene 
biguanide/sodium percarbonate against Chlorella vulgaris and Oscillatoria 
sp. verus time and pH 7.0. 
______________________________________ 
CONCENTRATION (ppm of each component) 
TIME(hrs) 50 60 80 90 100 
______________________________________ 
Chlorella Vulgaris 
2 90.0 95.0 100.0 100.0 
100.0 
4 90.0 95.0 100.0 100.0 
100.0 
6 100.0 100.0 100.0 100.0 
100.0 
Oscillatoria sp. 
2 50.0 60.0 75.0 100.0 
100.0 
4 75.0 75.0 100.0 100.0 
100.0 
6 90.0 100.0 100.0 100.0 
100.0 
______________________________________ 
ADDITIONAL EXAMPLE V 
__________________________________________________________________________ 
ANTIMICROBIAL ACTIVITY OF SOLUTIONS OF ONAMER M OR IL-779 WITH AND 
WITHOUT 
ADDITION OF HYDROGEN PEROXIDE AFTER CONTACT TIMES OF 0.5, 3 AND 6 HOURS 
Test Compounds* 
Ratio S. aureus 
Str. faecalis 
Ps. aeruginosa 
E. Coli C. Albicans 
S. cerevesiae 
(Percent Solids) 
Compound/ 
ATCC #6538 
ATCC #7080 
ATCC #15442 
ATCC #15221 
ATCC #10231 
ATCC #560 
H.sub.2 O.sub.2 
H.sub.2 O.sub.2 
EARLIEST DETECTED KILLING TIME, HOURS OF 
__________________________________________________________________________ 
CONTACT 
Onamer M 
0.025% 0.025% 
1/1 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 
0.000% 
1/0 &lt;0.5 3 &lt;0.5 &lt;0.5 &lt;0.5 3 
0.01% 0.01% 
1/1 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 
0.005% 
2/1 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 
0.00 
1/0 &lt;0.5 3 &lt;0.5 &lt;0.5 &lt;0.5 3 
IL-779 
0.025% 0.025% 
1/1 &lt;0.5 &lt;0.5 &lt; 0.5 &lt;0.5 &lt;0.5 &lt;0.5 
0.000% 
1/0 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 
0.01% 0.01% 
1/1 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 
0.005% 
2/1 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 
0.00% 
1/0 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 &lt;0.5 3 
H.sub.2 O.sub.2 ONLY 
0.025% 3 &gt;6 6 6 &gt;6 &gt;6 
0.01% 3 &gt;6 6 6 &gt;6 &gt;6 
0.005% 6 &gt;6 6 &gt;6 &gt;6 &gt;6 
__________________________________________________________________________ 
*Concentrations based on percent solids content of original solutions 
While the mechanism of potentiation of the biocidal activity of germicidal 
polymeric nitrogen compounds used in the aqueous composition of the 
invention is not completely understood at present, it is believed that 
these germicidal nitrogen polymers oxidize in situ at an N--H bond or at 
the alpha hydrogen in the R--CH.sub.2 --N group to produce small amounts 
of low molecular weight components such as aldehydes which are themselves 
excellent germicides. These aldehydes may be produced, for example, 
through a halogen oxidation to produce an --NX intermediate which in 
aqueous solution generates the aldehyde, or by direct oxidation of an 
alpha CH.sub.2 group to provide the aldehyde. In both cases, an oxidizing 
agent having a standard reduction potential of at least 0.85 volts and 
less than 2.0 volts has sufficient strength to effect the desired 
oxidation of such nitrogen polymers without decomposing the polymer. 
Furthermore, as organisms are being killed by the anti-microbial 
composition, oxidation of polymer can continue in situ to generate more of 
the highly active oxidization product.