U.S. patent number RE36,064 [Application Number 08/052,641] was granted by the patent office on 1999-01-26 for disinfection method and composition therefor.
This patent grant is currently assigned to Alcide Corporation. Invention is credited to Eugene A. Davidson, Robert D. Kross.
United States Patent |
RE36,064 |
Davidson , et al. |
January 26, 1999 |
Disinfection method and composition therefor
Abstract
There is disclosed, in one aspect, chlorous acid generating
compositions useful for disinfecting substrates. The compositions
comprise aqueous solutions containing a suitable amount of a protic
acid, such as citric or malic acid, and a suitable amount of a
metal chlorite, such as sodium chlorite. The chlorite ion
concentration which is in the form of chlorous acid in the
composition is no more than about 15 percent by weight of the total
amount of chlorite ion concentration. In a preferred embodiment,
the composition also contains a vicinal dihydroxy or polyhydroxy
compound. In another preferred embodiment, the composition contains
at least a 10-fold molar excess of a water soluble chloride ion
compared to the total concentration of chlorite ion. In another
aspect, there is disclosed a process for disinfecting substrates.
This process comprises applying the compositions described above to
a substrate. In yet another aspect, there is disclosed a process
for preparing the compositions described above. This process
comprises contacting the protic acid with the metal chlorite to
form the disinfecting composition.
Inventors: |
Davidson; Eugene A.
(Washington, DC), Kross; Robert D. (Bellmore, NY) |
Assignee: |
Alcide Corporation (Redmond,
WA)
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Family
ID: |
27411285 |
Appl.
No.: |
08/052,641 |
Filed: |
April 23, 1993 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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420651 |
Oct 11, 1989 |
4986990 |
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850009 |
Apr 10, 1986 |
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790436 |
Oct 23, 1985 |
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591787 |
Mar 21, 1984 |
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Reissue of: |
618729 |
Nov 27, 1990 |
05185161 |
Feb 9, 1993 |
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Current U.S.
Class: |
424/665 |
Current CPC
Class: |
A01N
59/00 (20130101); A01N 59/00 (20130101); A01N
2300/00 (20130101) |
Current International
Class: |
A01N
59/00 (20060101); A61K 033/14 () |
Field of
Search: |
;424/665,661 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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959238 |
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Dec 1974 |
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CA |
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965699 |
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Apr 1975 |
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CA |
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2 329 753 |
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Dec 1973 |
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DE |
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58-18617 |
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Jul 1981 |
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JP |
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58-18616 |
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Feb 1983 |
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JP |
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158180 |
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Jun 1972 |
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NZ |
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496247 |
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Nov 1938 |
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GB |
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880507 |
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Oct 1961 |
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GB |
|
Other References
Chemical Abstracts No. 80:74331g (1974). .
Chemical Abstracts No. 68:45873g (1968). .
Gordon et al., "The Chemistry of Chlorine Dioxide," Prog. Inorg.
Chem. 15:201, 1972. .
Abstract (21 P 192) (JP Patent Kokai No. 58-18617)..
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Primary Examiner: Criares; Theodore J.
Attorney, Agent or Firm: Seed and Berry LLP
Parent Case Text
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of U.S. patent application Ser.
No. 07/420,651, filed Oct. 11, 1989, now U.S. Pat. No. 4,986,990,
which is a continuation of U.S. patent application Ser. No.
06/850,009, filed Apr. 10, 1986, now abandoned, which is a
continuation-in-part of U.S. Ser. No. 06/790,436, filed Oct. 23,
1985, now abandoned which is an continuation of U.S. Ser. No.
06/591,787, filed Mar. 21, 1984, now abandoned.
Claims
We claim:
1. A process for disinfecting a substrate comprising contacting
said substrate with an aqueous solution consisting essentially of
from about 0.01% to about 6% by weight of an organic acid, wherein
the pK of the organic acid is from about 2.8 to about 4.2, and
wherein the organic acid is not lactic acid, and from about 0.0001%
to about 0.45% by weight based upon the total weight of said
composition of a metal chlorite, such that the chlorite ion
concentration in the form of chlorous acid is not more than about
15% by weight of the total amount of chlorite ion
concentration.
2. The process of claim 1 wherein the metal chlorite is sodium
chlorite.
3. The process of claim 1 wherein the organic acid is selected from
the group consisting of citric acid, malic acid, tartaric acid,
glycolic acid, mandelic acid, salicyclic acid, carbonic acid, and
combinations thereof.
4. The process of claim 1 wherein the organic acid is citric
acid.
5. A process for disinfecting a substrate comprising contacting
said substrate with an aqueous solution consisting essentially of
from about 0.01% to about 6% by weight glycolic acid, and from
about 0.01% to about 0.45% by weight based upon the total weight of
said composition of a metal chlorite, such that the chlorite ion
concentration in the form of chlorous acid is not more than about
15% by weight of the total amount of chlorite ion
concentration.
6. The process of claim 5 wherein glycolic acid ranges from about
0.05% to about 3% by weight of the total composition.
7. The process of claim 5 wherein glycolic acid ranges from about
0.1% to about 2% by weight of the total composition.
8. The process of claim 5 wherein the metal chlorite ranges from
about 0.03% to about 0.3% by weight of the total composition.
9. The process of any one of claims 5-8 wherein the metal chlorite
is sodium chlorite.
10. The process of claim 1 wherein the substrate is selected from
skin, tissue, body fluids and mucous membranes.
11. A process for disinfecting a substrate comprising contacting
said substrate with an aqueous solution consisting essentially of
from about 0.01% to about 6% by weight of an organic acid, wherein
the pK of the organic acid is from about 2.8 to about 4.2, and
wherein the organic acid is not lactic acid, and from about 0.01%
to about 0.45% by weight based upon the total weight of said
composition of a metal chlorite, such that the chlorite ion
concentration in the form of chlorous acid is not more than about
15% by weight of the total amount of chlorite ion
concentration.
12. The process of claim 11 wherein the organic acid ranges from
about 0.05% to about 3% by weight of the total composition.
13. The process of claim 11 wherein the organic acid ranges from
about 0.1% to about 2% by weight of the total composition.
14. The process of claim 11 wherein the metal chlorite ranges from
about 0.03% to about 0.3% by weight of the total composition.
15. The process of any one of claims 11-14 wherein the metal
chlorite is sodium chlorite.
16. The process of any one of claims 11-14 wherein the organic acid
is selected from the group consisting of citric acid, malic acid,
tartaric acid, glycolic acid, mandelic acid, salicylic acid,
carbonic acid, and combinations thereof.
17. The process of claim 11 wherein the substrate is selected from
skin, tissue, body fluids and mucous membranes.
18. A chlorous acid generating composition comprising an aqueous
solution consisting essentially of from about 0.01% to about 6% by
weight of an organic acid, wherein the pK of the organic acid is
from about 2.8 to about 4.1, and wherein the organic acid is not
lactic acid, and from about 0.0001% to about 0.45% by weight based
upon the total weight of said composition of a metal chlorite, such
that the chlorite ion concentration in the form of chlorous acid is
not more than about 15% of weight of the total amount of chlorite
ion concentration.
19. The composition of claim 18 wherein the metal chlorite is
sodium chlorite.
20. The composition of claim 18 wherein the organic acid is
selected from the group consisting of citric acid, malic acid,
tartaric acid, glycolic acid, mandelic acid, salicylic acid,
carbonic acid, and combinations thereof.
21. The composition of claim 18 wherein the organic acid is citric
acid.
22. A chlorous acid generating composition comprising an aqueous
solution consisting essentially of from about 0.01% to about 6% by
weight of an organic acid, wherein the pK of the organic acid is
from about 2.8 to about 4.2, and wherein the organic acid is not
lactic acid, and from about 0.01% to about 0.45% by weight based
upon the total weight of said composition of a metal chlorite, such
that the chlorite ion concentration in the form of chlorous acid is
not more than about 15% by weight of the total amount of chloride
ion concentration.
23. The composition of claim 22 wherein the organic acid ranges
from about 0.05% to about 3% by weight of the total
composition.
24. The composition of claim 22 wherein the organic acid ranges
from about 0.1% to about 2% by weight of the total composition.
25. The composition of claim 22 wherein the metal chlorite ranges
from about 0.03% to about 0.3% by weight of the total
composition.
26. The composition of any one of claim 22-25 wherein the metal
chlorite is sodium chlorite.
27. The composition of any one of claim 22-25 wherein the organic
acid is selected from the group consisting of citric acid, malic
acid, tartaric acid, glycolic acid, mandelic acid, salicyclic acid,
carbonic acid, and combinations thereof.
28. A chlorous acid generating composition comprising an aqueous
solution consisting essentially of from about 0.01% to about 6% by
weight glycolic acid, and from about 0.01% to about 0.45% by weight
based upon the total weight of said composition of a metal
chlorite, such that the chlorite ion concentration in the form of
chlorous acid is not more than about 15% by weight of the total
amount of chlorite ion concentration.
29. The composition of claim 28 wherein glycolic acid ranges from
about 0.05% to about 3% by weight of the total composition.
30. The composition of claim 28 wherein glycolic acid ranges from
about 0.1% to about 2% by weight of the total composition.
31. The composition of claim 28 wherein the metal chlorite ranges
from about 0.03% to about 0.3% by weight of the total
composition.
32. The composition of any one of claims 28-31 wherein the metal
chloride is sodium chlorite. .Iadd.
33. A process for disinfecting a substrate comprising contacting
said substrate with an aqueous composition consisting essentially
of a mixture of from about 0.01% to about 6% based upon the total
weight of said composition of a protic acid, wherein the protic
acid is not lactic acid, and from about 0.0001% to about 0.45% by
weight based upon the total weight of said composition of a metal
chlorite, such that the chlorite ion concentration in the form of
chlorous acid is not more than about 15% by weight of the total
amount of chlorite ion concentration..Iaddend..Iadd.34. The process
of claim 33 wherein the erotic acid ranges from about 0.05% to
about 3% by weight of the total composition..Iaddend..Iadd.35. The
process of claim 33 wherein the protic acid ranges from about 0.1%
to about 2% by weight of the total composition..Iaddend..Iadd.36.
The process of claim 33 wherein the metal chlorite ranges from
about 0.01% to about 0.45% by weight of the total
composition..Iaddend..Iadd.37. The process of claim 33 wherein the
metal chlorite ranges from about 0.03% to about 0.3% by weight of
the total composition..Iaddend..Iadd.38. The process of claim 33
wherein the metal chlorite is sodium chlorite..Iaddend..Iadd.39. A
chlorous acid generating composition comprising an aqueous
composition consisting essentially of a mixture of from about 0.01%
to about 6% based upon the total weight of said composition of a
protic acid, wherein the protic acid is not lactic acid, and from
about 0.0001% to about 0.45% by weight based upon the total weight
of said composition of a metal chlorite, such that the chlorite ion
concentration in the form of chlorous acid is not more than about
15% by weight of the total amount of chlorite ion
concentration..Iaddend..Iadd.40. The composition of claim 39
wherein the protic acid ranges from about 0.05% to about 3% by
weight of the total composition..Iaddend..Iadd.41. The composition
of claim 39 wherein the protic acid ranges from about 0.1% to about
2% by weight of the total composition..Iaddend..Iadd.42. The
composition of claim 39 wherein the metal chlorite ranges from
about 0.01% to about 0.45% by weight of the total
composition..Iaddend..Iadd.43. The composition of claim 39 wherein
the metal chlorite ranges from about 0.03% to about 0.3% by weight
of the total composition..Iaddend..Iadd.44. The composition of
claim 39 wherein the metal chlorite is sodium chlorite..Iaddend.
Description
BACKGROUND OF THE INVENTION
This invention relates generally to compositions for disinfecting
substrates as well as to processes for preparing and using such
compositions.
The term "disinfectant" is used in this specification to broadly
include any substance or composition that disinfects, sanitizes,
deodorizes, sterilizes, or kills germs.
The use of chlorine compounds in various types of disinfectant
compositions is well known. Chlorine compounds suggested for use in
this regard include, for example, sodium hypochlorite, used in
World War I as a wound irrigant, and chlorinated phenols such as
m-chlorophenol. These compounds have increased bactericidal
activity and reduced toxicity, in some instances, when compared to
non-chlorinated phenols. Thus, m-chlorophenol has a phenol
coefficient of 5.8 (S. aureus) to 7.4 (B. typhosus). Other chlorine
compounds having some form of disinfectant utility include, for
example, chlorine gas itself, chlorine dioxide, chloramine T,
calcium hypochlorite (a standard swimming pool disinfectant),
chloropicrin (a larvicide), chloroform (a fumigant), chlordane (an
insecticide), and chloromycetin (an antibiotic).
Chlorine dioxide in particular has been found to be an especially
effective disinfectant. This compound is quite versatile and has
long been used as a bleaching agent such as in the oxidizing of the
natural colorant present in cotton, wood pulp and other cellulosic
fibrous material. In such uses, chlorine dioxide, though performing
an oxidizing function, is nevertheless non-injurious with respect
to the fibrous material.
Additionally, chlorine dioxide has long been used in the treatment
of water supplies and a precursor is currently available
commercially in powder form for use in swimming pools and in liquid
form for household and industrial cleaning and disinfecting. In
general, chlorine dioxide is superior to gaseous chlorine in the
removal of odors and tastes, and in destroying and removing algae
or other organic material. Moreover, chlorine dioxide is considered
at least as effective as, if not superior to, chlorine gas as a
bactericide, virucide or sporicide. Chlorine dioxide is further
advantageous in that its antiseptic properties are not as sensitive
to pH as chlorine-i.e., chlorine dioxide retains its disinfectant
capacity to a significantly greater extent and over a wider pH
range than does gaseous chlorine.
Despite the manifold advantages associated with the use of chlorine
dioxide for the aforedescribed and related purposes, certain
difficulties are nevertheless encountered in practice. Thus,
chlorine dioxide as a concentrated gas is explosive and poisonous
and accordingly is usually not shipped in the gaseous state to the
medium or small user. It has thus become common practice to employ
a chlorine dioxide-liberating compound such as sodium chlorite
powder which is much safer from the standpoints of storage,
shipping and handling. Generation of the chlorine dioxide from
sodium chlorite or other chlorine dioxide liberating compound is
usually effected by addition of acid, bleach (hypochlorite), or
chlorine to the chlorine dioxide liberating compound.
The acid generation of chlorine dioxide is generally effected with
the use of a relatively inexpensive inorganic acid, e.g.,
hydrochloric acid, sulfuric acid and the like. Other acids such as
phosphoric or acetic acid (vinegar) have also been used.
Canadian Patent 959,238 to Callerame discloses such a conventional
method of producing chlorine dioxide by reacting an alkali metal or
alkaline earth metal chlorite, such as sodium chlorite, with an
acid. In general, any acid may be used including strong acids such
as sulfuric acid and hydrochloric acid and relatively weak acids
such as citric and tartaric. This conventional method of producing
chlorine dioxide (ClO.sub.2) uses relatively high concentrations of
chlorite and acid. The composition formed by this method is
advantageous only for the immediate disinfection of a
substrate-i.e, it does not result in a stable chlorine dioxide
generating solution but instead provides a rapid generation of
chlorine dioxide.
Acid-induced generation of chlorine dioxide from sodium chlorite as
heretofore recommended and practiced has proven ineffective in that
chlorine dioxide is not generated over an extended period of time.
On the contrary, these compositions result in a relatively short
concentrated period of chlorine dioxide generation and, once this
gas dissipates, the residual system is not useful for disinfection
purposes. One approach to compensate for this deficiency, and
retain significant residual chlorine dioxide in solution formore
prolonged activity is to use a system having an increased
concentration of sodium chlorite and acid. This approach, however,
may lead to toxicity problems, particularly when the composition is
used in an enclosed air space. In addition, such a system would be
inefficient, since the amount of chlorine dioxide produced greatly
exceeds the amount needed for disinfection.
Another problem stems from the fact that the composition obtained
from the interaction of the relatively high concentrations of
sodium chlorite and acid materials used in the past can be
injurious to health. Significantly, the toxicity problem imposes
severe limitations on the general utility of the disinfectant
composition, particularly with respect to the treatment of human
beings.
These prior methods result in the nearly complete and rapid
conversion of the majority of the chlorite precursor to chlorine
dioxide which is then used as a gas, or in solution.
The above-noted problems with using chlorine dioxide as a
disinfectant were solved to some extent by the use of a composition
comprising a water soluble chlorite, such as sodium chlorite, and
lactic acid. As disclosed in U.S. Pat. No. 4,084,747 to Alliger,
this particular composition possesses improved disinfectant
properties, properties not attained by using the same composition
but replacing the lactic acid with other acids such as phosphoric
acid, acetic acid, sorbic acid, fumaric acid, sulfamic acid,
succinic acid, boric acid, tannic acid, and citric acid. It would
be preferable from the standpoint of economics and acid
availability to be able to use acids other than lactic acid, still
obtain disinfectant utility, and maintain control over the rate of
formation of chlorous acid and thereby chlorine dioxide.
The search has continued for improved compositions for disinfecting
various germ carrying substances and improved disinfectant methods.
This invention was made as a result of that search.
OBJECTS AND SUMMARY OF THE INVENTION
Accordingly, it is a general object of the present invention to
avoid or substantially alleviate the above-identified problems of
the prior art.
A more specific object of the present invention is to provide
improved sanitizing, disinfecting and sterilizing compositions.
A further object of the invention is to provide such disinfecting
compositions having negligible toxicity under conditions normally
prescribed for use and thus highly useful in the germicidal
treatment of substrates such as food receptacles and utensils,
medical hardware, human or animal skin, and the like.
A further object of the present invention is to provide a process
for disinfecting various substrates.
An additional object of the present invention is to provide a
process for disinfecting substrates using compositions having
negligible toxicity and controlled stability over a relatively wide
pH range.
Other objects and advantages of the present invention will become
apparent from the following summary of the invention and
description of the preferred embodiments.
In one aspect, the present invention provides a composition for
disinfecting a substrate using a chlorous acid generating
composition. This composition comprises an aqueous solution
containing a suitable amount of a protic acid, and a suitable
amount of a metal chlorite. The chlorite ion concentration in the
form of chlorous acid is no more than about 15 percent by weight of
the total amount of chlorite ion concentration. The composition
contains substantially no lactic acid, preferably no lactic acid at
all.
In a preferred embodiment of this aspect of the present invention,
there is provided a composition for disinfecting a substrate with a
composition comprising a chlorous acid generating compound with a
sufficient amount of a suitable organic acid to lower the pH of the
composition to less than about 7. The suitable organic acid has the
formula: ##STR1## R.sup.1 and R.sup.2 may be the same or different
and may be selected from the group consisting of hydrogen, methyl,
--CH.sub.2 COCH, --CH.sub.2 OH, --CHOHCOOH, and --CH.sub.6 H.sub.5.
The pK of the organic acid is from about 2.8 to about 4.2. The
composition contains substantially no lactic acid.
In a particularly preferred embodiment, the present invention
provides a synergistic composition for disinfecting a substrate.
This composition comprises
(a) a chlorine dioxide liberating compound:
(b) a sufficient amount of the suitable organic acid described
above to lower the pH of the composition to less than about 7;
and
(c) a vicinal dihydroxy or polyhydroxy compound.
In another aspect, the present invention provides processes for
disinfecting a substrate using the compositions described above.
These processes comprise applying the compositions described above
to a substrate in order to disinfect the substrate.
In yet another aspect, the present invention provides process for
preparing these disinfecting compositions. This process comprises
contacting the protic acid with the metal chlorite to form the
disinfecting composition.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
As noted above, the present invention is directed to a chlorous
acid generating composition for disinfecting a substrate. The
composition comprises an aqueous solution containing a suitable
amount of a protic acid, and a suitable amount of a metal chlorite
such as sodium chlorite. The concentrations of chlorite and acid
are relatively low and are such that the amount of the chlorite in
the form of chlorous acid is no more than about 15 percent by
weight of the total chlorite ion concentration in solution.
Typically the amount of the chlorite in the form of chlorous acid
is no more than about 10 percent by weight of the total chlorite
ion concentration in solution.
The percent by weight of chlorite and chlorous acid may be
calculated from the ionization constant of chlorous acid and the
amount of hydrogen ion in solution produced by the partial
ionization of the protic acid. Thus the hydrogen ion concentration,
[H.sup.+ ], in a solution of the protic acid, HA, of known molar
concentration and whose ionization constant is K.sub.A, may be
calculated from the following relationship: ##EQU1## This same
relationship may be applied to calculate the relative chlorite and
chlorous acid concentrations where the ionization constant for
chlorous acid is 1.1.times.10.sup.-2. That is: ##EQU2## where the
hydrogen ion concentration, [H.sup.+ ], is the quantity already
determined by ionization of the known amount of the protic acid,
HA. This calculation is well known to those skilled in this
art.
The composition of this invention provides a metastable chlorous
acid composition formed from relatively small amounts of chlorite
and acid. This composition is capable of generating chlorine
dioxide over a long period of time at continuing levels of
effectiveness. As chlorine dioxide forms, more of the chlorite
converts to chlorous acid by interacting with hydrogen ions further
generated by ionization of the protic acid.
The compositions of this invention are therefore different from
many prior art compositions which consist of relatively high
concentrations of chlorite and acid. The prior art compositions
result in the rapid conversion of chlorous acid to chlorine
dioxide. The rate of chlorine dioxide formation depends on the sum
of the square of chlorous acid concentration and the product of
chlorous acid and chlorite concentrations according to the equation
##EQU3## See Gordon, "The Chemistry Of Chlorine Dioxide", 15 Prog.
Inorg. Chem. 201 (1972).
Thus the rate at which chlorine dioxide forms depends exponentially
on the amount of chlorite ion which is converted to chlorous acid
and the amount of chlorite ion present.
In certain embodiments of the invention, the chlorous acid
generating composition comprises an aqueous solution containing
generally from about 0.01 to about 1, typically from about 0.02 to
about 0.5, and preferably from about 0.03 to about 0.3 percent by
weight of metal chlorite and a suitable amount of an organic acid
having a pK of from about 2.8 to about 4.2. The pH of this
composition is generally less than about 7, typically from about
2.2 to about 7.0.
In yet another embodiment of this invention, even lower
concentrations of chlorite and acid may be used in the composition.
These compositions comprise an aqueous solution containing
generally up to about 0.3, and typically from about 0.0001 to about
0.03 percent by weight of metal chlorite, and a suitable amount of
acid having a pK of from about 2.8 to about 4.2. The pH of the
composition is generally less than about 7, typically from about
2.2 to about 7.0.
In certain embodiments of the invention, an acid is used of the
formula ##STR2## wherein R.sup.1 and R.sup.2 may be the same or
different and may be selected from the group consisting of
hydrogen, methyl, --CH.sub.2 COOH, --CH.sub.2 OH, --CHOHCOOH and
--C.sub.6 H.sub.5.
Other embodiments of the invention may be formulated for a specific
disinfecting procedure or as a result of a specific production
method. These embodiments may contain an acid component, e.g.
salicylic acid or carbonic acid, which is specifically suited for
that procedure or production method.
Optionally the compositions of the invention may contain either a
suitable amount of a compound containing vicinial hydroxy groups or
an amount of a water soluble chloride in a significant molar excess
to the chlorite, or both. These optional ingredients facilitate the
formation of chlorine dioxide from chlorous acid and are thus
useful in rapidly disinfecting compositions where an increased rate
of chlorine dioxide formation is desired while maintaining a low
concentration of chlorite and acid.
The metal chlorite useful in the present composition may more
generally be described as a chlorine dioxide liberating compound.
By "chlorine dioxide liberating compound" is meant any compound
which, when appropriately treated, effects the production of
chlorine dioxide as a result of a change in the valence state of
the chlorine atom from +3 to +4. While any chlorine dioxide
liberating compound may be used, water-soluble chlorites are
preferred because they are readily available and inexpensive.
Typical water-soluble chlorites include metal chlorites, such as
alkali metal chlorites and alkaline earth metal chlorites. Sodium
chlorite and potassium chlorite are preferred. Sodium chlorite is
particularly preferred.
The disinfectant composition may be used in conjunction with an
application medium. The application medium may be any compatible
medium including a gel or a liquid such as water. An aqueous
application medium is preferred. The application medium may contain
other additives such as chelating agents (eg., Na.sub.4 EDTA),
surfactants (e.g., Pluronic F68 nonionic polyoxyalkylene or
Nacconol alkylaryl sulfonate), or preservatives (e.g., sodium
benzoate).
The amount of chlorine dioxide liberating compound that may be used
in this composition may be generally from about 0.01% to about 1%,
typically from about 0.02% to about 0.5%, and preferably from about
0.03% to about 0.3% by weight of the total composition (including
the application medium).
At chlorite ion levels higher than about 0.5%, the concentration of
chlorous acid formed upon admixture of a protic acid may be in
excess of that required for the formation of a metastable chlorous
acid solution. These higher concentrations of chlorous acid would
cause the formation of chlorine dioxide, through the degradation of
chlorous acid at too rapid a rate.
Any protic acid may be used in the present invention so long as the
chlorite ion concentration limits described above are met. Suitable
organic acids include citric, malic, tartaric, glycolic, mandelic
or other structurally similar acids as described in Formula I
hereinabove.
The pK of these organic acids may be generally from about 2.8 to
about 4.2, and preferably from about 3.0 to about 4.0.
Salicylic acid and carbonic acid may also be used.
The amount of organic acid used in these compositions should be
sufficient to lower the pH of the composition to less than about 7,
typically from about 2 to about 5, and preferably from about 2.2 to
about 2.7. Furthermore, this amount may be generally from about
0.01% to about 6%, typically from about 0.05% to about 3%, and
preferably from about 0.1% to about 2% by weight of the total
composition (including the application medium).
A suitable amount of a vicinal dihydroxy or polyhydroxy compound
may also be added to the compositions of the present invention. The
use of such compositions enables one to produce compositions
according to the invention which are more rapidly effective in
higher pH ranges. The use of these vicinal dihydroxy or polyhydroxy
compounds also allows for the use of compositions according to the
invention which contain a much lower acid concentration than that
which is needed if the vicinal polyhydroxy compound comprising at
least two vicinal hydroxy groups is absent.
Vicinal polyhydroxy compounds which contain at least two vicinal
hydroxy groups are well known to those skilled in this art and
include dextrose and other sugars, glycerin, sorbitol, inositols,
and 1,2-propylene glycol. It is preferred that sugars with vicinal
hydroxy groups in the cis configuration such as galactose, mannose,
and ribose be used.
The use of such vicinal polyhydroxy compounds, particularly those
with cis-vicinal hydroxy groups, in conjunction with the chlorine
dioxide liberating compound and organic acid results in a
synergistic composition. The vicinal dihydroxy or polyhydroxy
compound catalyzes the formation of chlorine dioxide from chlorous
acid. For example, the rate of formation of the active chlorine
dioxide entity using a composition comprising sodium chlorite and
mandelic acid is substantially enhanced by the addition of a
relatively insubstantial amount of a vicinal polyhydroxy compound
Thus, the use of as little as 0.1% ribose in the composition
substantially enhances the rate of formation of the active entity
vis-a-vis a composition containing only sodium chlorite and one of
the organic acids discussed hereinabove.
Stated otherwise, a composition containing the vicinal polyhydroxy
compound may be prepared having substantially the same initial
germ-killing efficiency in a specified time period as a composition
which does not contain the vicinal polyhydroxy compound even though
the composition containing the polyhydroxy compound contains
substantially much less organic acid and sodium chlorite. However,
such activation of the system results in a more rapid depletion of
the chlorite ion in the composition, so that the germ-killing
activity at a later time period would be less.
The amount of vicinal polyhydroxy compound containing at least two
vicinal hydroxy groups may vary widely, but in the present
invention there is employed generally less than about 20%,
typically from about 0.1% to about 10%, and preferably from about
0.2% to about 2% by weight of the total composition.
Alternatively, or in addition, the composition may contain a large
excess of chloride ion in the form of an alkali or an alkaline
earth metal salt. The excess may be from about a 10 to about a 100
fold excess by weight of chloride ion over total chlorite ion
concentration. Large excesses of chloride ion in acid solutions
(below a pH of about 7) cause the chlorite ion to decompose in an
accelerated manner, via the formation of chlorous acid to form
chlorine dioxide In a preferred embodiment of the invention where
rapid disinfection is required, the composition contains both a
high excess of chloride ion and a sufficient amount of a vicinal
polyhydroxy compound comprising at least two vicinal hydroxy
groups.
The chlorine dioxide liberating compound is generally kept separate
from the organic acid prior to use in order to avoid premature
reaction of the ingredients.
The above-described compositions may be used to disinfect various
substrates. The term "substrate" as used in the instant
specification is intended to cover any type of surface or carrier
which could provide a locus for the accumulation of germs (viruses,
yeasts, bacteria, fungi, i.e, all types of microorganisms). Obvious
examples include surgical and dental instruments, foods, food
containers, human and animal skin, tissue body fluids and mucous
membranes, swimming pools, household sinks, garbage containers,
bathroom appliances, etc.
Cleaning action may be enhanced by the addition of a wetting agent,
the latter being compatible with and devoid of any tendency to
react with chlorite, chlorous acid or chlorine dioxide.
Particularly effective wetting agents for such use are anionic
surfactants which are commercially available. The instant
compositions in aerosol form may be effectively used to destroy
airborne or atmospheric germs such as those carried within an
enclosed air space.
When these compositions are used on human or animal skin, they may
also be typically applied in conjunction with a gel application
medium because of the ability of the gel to adhere to the skin. Any
gelling agent or thickener which is non-toxic and non-reactive with
the chlorine dioxide-liberating compound and organic acid may be
used. Cellulose gels, particularly methyl and hydroxyethyl
cellulose gels, polyvinylsulfonic acid, polyamide and silica-based
gels, are preferred. Preservatives may also be used when the gel
form is employed. For example, sodium benzoate may be used as a
preservative in the organic acid gel.
The amount of thickener which may be used in the gel varies
depending upon the intended application, the particular acid, the
chlorine dioxide liberating compound, and the other additives
employed. However, the amount may be generally from about 1 to
about 30, typically from about 4 to about 20, and preferably from
about 4 to about 6, percent by weight of the total composition. The
amount of preservative in the total composition may be generally
from about 0.01 to about 0.05, typically from about 0.01 to about
0.04, and preferably from about 0.02 to about 0.03, percent by
weight of the total composition.
When the chlorine-dioxide liberating compound and organic acid are
present in separate gels, the amounts of each present in the
respective gels are adjusted so that when the gels are mixed the
specified percentages will be present in the resulting composition.
For example, when the gels are designed to be mixed in equal parts,
which is preferred, the amount of chlorine dioxide liberating
compound present in the first gel may be generally from about 0.02%
to about 2%, typically from about 0.05% to about 1%, and preferably
from about 0.1% to about 0.6% by weight of the first gel. The
amount of organic acid present in the second gel may be from about
0.1% to about 12%, typically from about 0.5% to about 10%, and
preferably from about 1% to about 6% by weight of the second
gel.
Additionally, when the chlorine dioxide liberating compound and
organic acid are present in separate gels, the preservative is
present in only that gel which contains the organic acid and the
thickener is present in both gels. The gel which contains the
chlorine dioxide liberating compound is preserved by suitable
alkaline pH adjustments.
Therefore, when the gels are designed to be mixed in equal parts,
the amount of preservative present in the second gel, the organic
acid gel, is generally from about 0.02% to about 0.1%, typically
from about 0.02% to about 0.08%, and preferably from about 0.04% to
about 0.06% by weight of the second gel. The amount of thickener
present in both the first and second gels depends on the gelling
agent and is generally from about 0.5 to about 15, and typically
from about 2 to about 10, and preferably from about 2 to about 3,
percent by weight of the individual gels.
These gels may be mixed just prior to application or may be
simultaneously mixed and applied in situ.
The compositions of this invention may be applied to various
substrates in a manner known to those skilled in this art. The
compositions may be sprayed, coated or applied in any other manner
depending upon the substrate being treated.
The compositions of this invention may be used for skin
applications, for example, by applying a small but effective amount
of the composition to the affected area of the skin using any means
known to those skilled in this art including, for example, an
applicator such as a cotton swab. The composition is allowed to
remain on the affected area for a sufficient period of treatment.
The composition may be reapplied to maintain an effective level of
the composition throughout the period of treatment.
For most skin applications, a frequency of one or two applications
provides relief. In most cases, the composition may be applied
liberally to the site, preferably as soon as possible after the
infection, disease, inflammation etc. appears. If liquid is
applied, a suitable applicator is a cotton gauze soaked with a
liquid formulation The lesion or affected area should be kept in
contact with the wet gauze for a few minutes.
When gel is used, it should be liberally applied. If the gel is
absorbed or accidentally removed, it may be reapplied as
necessary.
These compositions may also be used in soap products, toothpastes,
mouthwashes, and the like.
In addition to the gel and solution form, the chlorine dioxide
liberating compound and the organic acid may also be provided in
powder form in two packets or in a two compartment single package
wherein the compartments are separated by a suitable seal. One
embodiment of such a package uses a water soluble, heat sealable,
polyvinyl-alcohol-cellulosic as the package material. Other
suitable packaging materials compatible with the composition
ingredients are well known to those skilled in this art.
The present invention is illustrated by the following Examples. All
parts and percentages in the Examples as well as the specification
and claims are by weight unless specified otherwise.
EXAMPLE I
This example illustrates the use of the present composition as a
mouthwash.
A first solution is prepared by dissolving 0.4 grams of technical
grade sodium chlorite, 0.17 grams of powdered Na.sub.4 EDTA-4H2O,
0.5 grams of 1-carvone (mint flavor) and the appropriate amount of
a compatible food grade yellow dye in 500 milliliters of aqueous
solution. A second solution is prepared by dissolving 1.375 grams
of anhydrous citric acid and the appropriate amount of FD&C
Blue #1 in a batch of 500 milliliters of a 10 percent by weight
aqueous solution of glycerin.
The two solutions are mixed, preferably just prior to use, in
substantially equal amounts and the mixture is used in the normal
manner as a mouthwash. This results in improved bacterial,
fungicidal, and taste properties over presently available
commercial antiseptic mouthwashes and may aid in plaque
reduction.
EXAMPLE II
This example illustrates the preparation of compositions capable of
very rapid disinfection of contact lenses The lens may be immersed
in the solutions of these compositions for several minutes, and
upon removal can be immediately and safely placed on the eye.
The contact lens disinfectant solutions comprise sodium chlorite
powder; citric (or equivalent) acid powder to convert sodium
chlorite to chlorous acid; sodium chloride in sufficient quantity
to render the final solution isotonic with tears and hasten the
degradation of chlorous acid to chlorine dioxide; and optionally a
sugar such as ribose which catalyzes the conversion of chlorous
acid to chlorine dioxide. Other optional ingredients, such as
polyvinyl alcohol or hydroxyethylcellulose, to modify the viscosity
of the final solution, may also be used.
With such a combination, the initial solution formed by dissolving
the materials in water will have a pH of less than about 4, but
will rise to a pH of over about 5 within ten minutes, and to a pH
of over about 6 within about one hour. This occurs because the
citric acid transfers ionizable hydrogen atoms to sodium chlorite
thereby forming chlorous acid and sodium dihydrogen citrate, Large
excess of chloride ion with respect to chlorite ion in acid
solutions (below about pH 7) cause the chlorite ion to decompose,
via the formation of chlorous acid, to form chlorine dioxide. In
the process the acidity of the solution decreases, and the pH
rises. Sugars such as ribose also catalyze the formation of
chlorine dioxide from chlorous acid, and also diminish the acidity
of the aqueous system. One of the end products of the formation of
chlorine dioxide from chlorous acid is chloride ion. The chloride
ion so formed increases the chloride ion pool already present and
further causes the chlorite ion to decompose.
The chlorine dioxide thus rapidly generated from this mixture in
combination with the remaining chlorite ion in this system provides
highly effective microbiocidal activity, and kills microorganisms
commonly found as contact lens contaminants.
The following two-part system, when combined in 50 ml of water,
killed over 10.sup.7 cfu/ml of Serratia marcescens, and over
10.sup.4 cfu/ml of Aspergillus fumigatus within 30 seconds.
______________________________________ Part A: 5.0 mg Sodum
chlorite 200.0 mg Sodium chloride Part B: 0.627 mg Citric acid,
anhydrous 200.0 mg Sodium chloride 250.0 mg Ribose
______________________________________
A contact lens placed in this prepared solution for only a few
minutes would be disinfected and could be, placed back in the eye,
with no further saline rinse, and with full comfort and safety.
The above solution could also be prepared by combining the
ingredients, without sodium chloride, in a preexisting saline
solution, and the results would be substantially the same.
If a sugar such as ribose were not used, a slightly higher level of
citric acid (or equivalent) could be used. The same type of pH rise
would occur, although more slowly, and the final pH would not be as
high (between about pH 4.5 and 5.5). In this embodiment, it may be
necessary to employ a subsequent sterile saline wash if it is
desired to reinsert the lens within a few minutes of
disinfection.
EXAMPLE III
This Example illustrates the use of the compositions of the present
invention as a unique therapeutic agent for the treatment of
acne.
Salicylic acid is currently used in topical acne agents as a
comedolytic agent. As a comedolytic, salicylic acid loosens and
strips away tissue from comedones, the plugged sebaceous gland
involved in the pathogenesis of acne.
The present invention uses salicylic acid, which has a pK of 2.97,
as a hydrogen ion source to convert some of the chlorite ion to
chlorous acid and then to the free-radical ClO.sub.2. The system
therefore provides in addition to the comedolytic activity of the
salicylic acid the bactericidal activity of the chlorine
dioxide/chlorous acid system.
In a preferred embodiment of the invention, the following two part
formulation is a composition useful for topically treating
acne:
______________________________________ Acne Gel Percent by Weight
______________________________________ Part I Salicylic Acid 2.0%
Isoporopyl Alcohol 30.0% Sodium Benzoate 0.04% Natrosol 250 MR 2.1%
Pluronic F68 0.4% Deionized Water q.s. Part II Rheothik 80-11 45.0%
Sodium hydroxide, 1N 38.0% Nacconol 90-F 1.8% Na.sub.4 EDTA (38%)
0.5% Sodium Chlorite (79%) 0.4% Deionized Water q.s.
______________________________________
Natrosol 250 MR is a variety of hydroxyethyl cellulose. Pluronic
F68 is a non-ionic surface active agent Rheothik 80-11 is a
polyvinylsulfonic acid gelling agent and Nacconol 90-F is an
anionic surface active agent. Other varieties of these optional
ingredients having the equivalent or similar properties may be
substituted in the above formulation and used in accordance with
the invention.
EXAMPLE IV
This example illustrates the preparation of carbonic acid
compositions.
Carbon Dioxide gas, when dissolved in water, forms carbonic acid,
i.e.
Carbonic Acid is capable of dissociating in water to provide
hydrogen ion and bicarbonate ion, i.e.
If a sodium chlorite solution is placed in a sealed vessel into
which a gas can be introduced under pressure, eg. a sealed soda
dispenser, and then a CO.sub.2 cartridge is expelled into the
solution, the above two reactions will ensue, and some liberated
hydrogen ion will react with the chlorite ion to form chlorous
acid, i.e.,
The chlorous acid, in the acid environment, will slowly
disproportinate to form the disinfecting material, chlorine
dioxide, by one of several reactions, e.g.,
Accordingly, by releasing this pressurized solution into the
environment, there is provided a disinfecting solution containing
chlorine dioxide. The pressurized solution is stable for at least
several weeks.
Not only can the solution be used to disinfect substrates, but the
solution itself is also disinfected. To illustrate, a CO.sub.2
cartridge, containing 5.36 grams of the compressed CO.sub.2 gas, is
discharged under its own pressure into one liter of solution
containing 0.0103 percent sodium chlorite. The pH of the solution,
prior to CO.sub.2 charging, is 6.45. At various times thereafter,
the level of ClO.sub.2 is measured spectrophotometrically. The pH
of the solution is also measured and these measurements are shown
in the Table below.
______________________________________ Time (hours) pH ClO.sub.2
(ppm) ______________________________________ 0 6.45 -- 4 4.85 1.1
24 (1 day) 4.2 1.7 96 (4 days) 4.0 2.7 240 (12 days) 4.0 5.0 336
(16 days) 4.0 8.8 ______________________________________
These concentrations of chlorine dioxide are highly effective for
destroying a wide range of bacteria, yeasts, fungi and viruses.
One specialized application of this system is in the disinfection
of contact lenses. Immersion of a contaminated lens, particularly a
hydrophilic lens, into such a solution for a few minutes may
destroy the contaminating organisms. If the chlorite solution
contained the appropriate amount of sodium chloride as well (i.e.
physiological saline), the disinfected lens could be placed in the
eye without a subsequent saline rinse. The chloride ion would also
hasten the conversion of the chlorite to chlorine dioxide. The
further addition to this mixture of a small quantity, e.g.
0.01-0.1%, of a vicinal cis-hydroxy sugar (e.g. ribose, galactose)
would additionally hasten the conversion of chlorite to
ClO.sub.2.
Another particular application of this embodiment is in the
preparation of potable water. By discharging a CO.sub.2 cartridge
into a pressure bottle containing water of suspect quality (e.g.
the water one might find during a camping trip), to which a small
amount of chlorite powder is added, a supply of potable water is
obtained. The quantity of chlorite powder is selected in order to
provide adequate disinfection without leaving levels of chlorite
which might be considered harmful, or providing levels of ClO.sub.2
of a similar nature. The addition of a small quantity of
cis-hydroxy sugar to provide more rapid and more complete
conversion of chlorite to ClO.sub.2 facilitates the use of lower
initial chlorite levels.
The principles, preferred embodiments and modes of operation of the
invention have been described in the foregoing specification. The
invention which is intended to be protected herein, however, is not
to be construed as limited to the particular forms disclosed, since
these are to be regarded as illustrative rather than restrictive.
Variations and changes may be made by those skilled in this art
without departing from the spirit of the invention.
* * * * *