Process and synergistic compositions for disinfection comprising a chlorine dioxide liberating compound and an alpha-hydroxyalkanoic acid derivative

Process and synergistic compositions for disinfection comprising a chlorine dioxide liberating compound and an a-hydroxyalkanoic acid derivative ftLCIDE CORPORATION'

C: 66668

BACKGROUND OF THE INVENTION

This invention relates genera 1.1y_J-.n_.compnnit-i oris 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, mercuric chloride, calcium hypochlorite (a standard swimming pool disinfectant), chloropicrin (a larvicide)., chloroform (a fumigant), chlordane (an insecticide), zinc chloride (a preservative) , and Chloromycetin Can 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. Thus, 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, tastes, and in destroying and removing algae or other organic material. Moreover, chlorine dioxide is considered at least as effective 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 obtainable 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 dioxideliberating 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 compounds is usually effected by addition of either 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.

Phosphoric or acetic acid (vinegar) is sometimes recommended for home use since they are comparatively safe to handle and generally readily available.

Canadian Patent 959,238 to Callerame discloses 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.

_Acid-induced generation of chlorine dioxide from sodium chlorite as heretofore recommended and practiced has proven ineffective for the most part., The composition resulting from acidification of the sodium chlorite does not usually exhibit the desired disinfectant efficacy, particularly from the standpoint of the rate of germ kill. To compensate for this deficiency, it becomes necessary to use an increased concentration of sodium chlorite and acid which may lead to toxicity problems, particularly when the composition is used in an enclosed air space.

Another problem stems from the fact that the composition obtained from the interaction of the sodium chlorite and acid material does not provide a truly effective solvent environment

74684/2 for the active chlorine containing products such as chlorine dioxide, chlorous acid and the like. Inhalation of these components to any significant extent can be injurious to health. Significantly, the toxicity problem imposes severe limitations on the general utility of the disinfectant composition, particularly with respect to treatment of human beings.

These prior methods result in the nearly complete and rapid conversion of the chlorite precursor to chlorine dioxide, which is then used as the gas or, less frequently, 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. Patent 4,084,747, to Alliger, this particular composition possesses improved disinfectant properties, properties not attained by using the same composition but wholly 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.

Previous attempts to achieve a stable disinfecting composition with the metal chlorite, sodium chlorite, have resulted in short acting disinfection because the active antimicrobial agent, chlorous acid, is an intermediate in the reaction to form chlorine dioxide. For example, Canadian Patent 959,238, to Callerame, refers to the use of sodium chlorite at a concentration of 1.35%. Moreover, Japanese Patent Application 58-18616, to Toray Ind., refers to a contact lens solution

4a consisting of 0.5% sodium chlorite and a range of citric acid concentrations.

In each case, the high chlorite concentration in the presence of an acid results in the formation of chlorous acid proportional to the chlorite concentration. Chlorous acid breaks down to form chlorine dioxide. The rate of chlorous acid breakdown to chlorine dioxide is second order and depends upon the square of the chlorous acid concentration according to the following differential equation:

dHC10₂

------- = K[HC1O₂]² + K׳[HC1O₂][Clo₂־] dt wherein t is time and K and K׳ are rate constants.

Therefore, the high chlorite concentrations disclosed in the Callerame and Toray references will increase the concentration of chlorous acid, which, in turn, will significantly increase the rate of chlorous acid breakdown to chlorine dioxide. Thus, the concentration of chlorous acid over time will be low and unable to achieve prolonged disinfection when the chlorite concentration is high.

The search has continued for improved compositions for disinfecting various germ carrying substances and improved disinfection 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 aboveidentified problems.

A more specific object of the present invention is to provide improved cleaning, sanitizing, and disinfecting 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 diseases, and the like.

Another object of the present invention is to provide such compositions having controlled stability over a relatively wide pH range.

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.

The present invention provides, in one aspect, a process for disinfecting a substrate. This process comprises contacting the substrate with a composition comprising:

(a) a chlorine dixoide liberating compound wherein the concentration of said chlorine dioxide liberating compound is from 0.01% to 0.3% based upon the total weight of said composition; and /2 (b) sufficient organic acid other than lactic acid to lower the pH of said composition to less than 7, said organic acid having the formula (I):

II C-OH * (I)

I rI-C-OH

I

R²wherein R¹ and R² are the same or different and are selected from the group consisting of hydrogen, methyl, phenyl, -CH2COOH, -CH20H, -CHOHCOOH, and -CH2C6H5, wherein the pK of said organic acid is from 2.8 to 4,2.

In another aspect, the present invention provides a composition for disinfecting a substrate, comprising a mixture of two solutions or gels, said first solution or gel consisting essentially of a chlorine dioxide liberating compound wherein the concentration of said chiorine dioxide liberating compound is from 0.01% to 0.3% based upon the total weight of said composition, and. said second solution or gel containing an organic acid other than lactic acid, to lower the pH of said mixture to less than 7, said organic acid having the formula:

II C-OH (I)

I Rl-C-OH

I

R²wherein R¹ and R² are the same or different ’ and are selected from the group consisting of hydrogen, methyl, phenyl, -CH₂COOH, -CH₂OH, -CHOHCOOH, and -CH₂C6^li5׳ wherein the pK of said organic acid is from 2.8 to 4.2.

In yet another aspect, the present invention provides a synergistic composition for disinfecting a substrate, which composition comprises, in addition to the mixture described above, also a vicinal polyhydroxy compound, wherein said vicinal polyhydroxy compound is different from the organic acid.

a74684/2 X'

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present composition employs a chlorine dioxide liberating compound as one of the components of the disinfectant composition. By chlorine dioxide liberating compound is meant any compound which when appropriately treated will liberate chlorine dioxide. 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 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

׳. 74684/2 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 (e.g., Na^EDTA), surfactants (e.g., Pluronic F68 or Nacconol alkylaryl sulfonate), or preservatives (e.g., sodium benzoate).

The amount of chlorine dioxide liberating compound that is used in this composition may be generally from about 0.01 to about 0.3% by weight ״of the.total composition (including the application medium).

The organic acid used in the _pre.s.en.t-invjsntion may be citric, malic, tartaric, glycolic, mandelic or other structurally similar acids as described in Formula I hereinabove. Mixtures of two or more such organic acids may also be used.

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.

The amount of organic acid used should be sufficient to lower the pH of the composition to less than about 7, typically from about i 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 I and preferably from about .0.1 to about 2.% by weight of the total composition (including the application medium!.

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.

In a preferred embodiment, the disinfectant composition contains a vicinal polyhydroxy compound, preferably a vicinal dihydroxy compound, and most preferably a dihydroxv compound with cis hydroxyl groups. Vicinal polyhydroxy compounds are well known to those skilled in this art and include dextrose and other sugars, such as xylose, galactose, mannose, lactose and ribose, hydroxyethyl cellulose, glycerin, sorbitol, inositols, and 1,2-propylene glycol.

The use of such vicinal polyhydroxy compounds in conjunction with the chlorine dioxide liberating compound and organic acid results in a synergistic composition. For example, the rate of formation of the active 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 2¾ dextrose 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 with the vicinal polyhydroxy compound may be prepared having substantially the same germ-killing efficacy in a specified time.period as a composition which does not contain the polyhydroxy compound even though the composition containing .the polyhydroxy compound contains substantially much less organic acid and sodium chlorite.

The amount of polyhydroxy compound may vary widely but in the present invention there is employed generally less than about 50, typically from about 1 to about 20., and preferably from about 2 to about 10 percent by we'ight of the total composition.

/2

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, virus, spores, bacteria, fungi, i.e., all types of parasitic microorganisms. Obvious examples include surgical and dental instruments, food containers, animal skin, animal tissue and mucous membranes (mouth tissue), 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 chlorine dioxide. Particularly effective wetting agents for such use are anionic surfactants which are commercially available. The instant compositions in aerosol fornrimay be effectively used to destroy airborne or atmospheric germs such as carried within an enclosed air space.

When these compositions are used on 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 cellulose gels, 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 in the gel varies depending upon the particular acid and chlorine dioxide liberating compound employed.

74684/2

However, the amount maybe generally from about 0.5 to about 8, typically from about 2 to about .3, and preferably from about 2.5 to about 2.7 percent by weight of the gel. The amount of preservative in the gel 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 iiv 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;

0.6 percent 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 percent 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.

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 percent by weight of the second gel and the amount of thickener present in both the first and i second gels is generally from about 0.5 to about 4, typically from about 2 to about 3, and preferably from about 2.5 to about 2.7 percent by weight of each gel.

These gels may be mixed just prior to application or may be simultaneously mixed and applied in situ.

A small but effective amount of the composition may be applied 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 irritations, 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 inflammation 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-cellulose as the package material. Other suitable packaging materials compatible with the composition ingredients are well known to those skilled in this art.

The package material may contain vicinal hydroxy groups and thus serve additionally as a synergist.

The present invention is illustrated by the following Example. All parts and percentages in the Example as well as the specification and claims are by weight unless specified otherwise.

EXAMPLE

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^EDTA . 4H_q0, 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 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 i.s used in the normal manner as a mouthwash. This results in improved bactericidal, fungicidal, and taste properties over presently available commercial antiseptic mouthwashes.

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.