Bactericidal composition

Abstract

The present invention relates to compositions having surprising bactericidal activity. The compositions of the present invention are aqueous compositions containing from 5 to 15 percent of an aliphatic monocarboxylic acid having from 8 to 11 carbon atoms, and the balance either a non-ionic or anionic detergent.

Description

BACKGROUND OF THE INVENTION

In the past 10 years hospital acquired gram negative bactericidal infections have risen significantly and have been one of the major causes of in-hospital patient deaths and patient morbidity requiring prolonged hospitalization.

Nosocomial gram negative bacteria are invariably resistant to currently available antibiotics. Attempts at controlling hospital acquired infection have centered on preventing colonization and tissue invasion by these organisms. At the present time there are few agents effective in preventing these infections.

Therefore, it is highly desirable to develop compositions which have strong bactericidal activity. In fact, compositions of this type have long been sought after for use as a general disinfectant or degerming agent or surgical scrub. For example, bactericidal compositions are widely used in hospitals, especially in surgical procedures and nurseries, as well as in the home.

For this general use, a bactericidal composition is subject to several stringent requirements. The composition must be relatively inexpensive in view of the widespread use to which it is subjected. Furthermore, the candidate composition must have a high degree of bactericidal activity against a wide variety of organisms, and should preferably be 100 percent effective within a short period of time against the organisms commonly encountered in hospitals. Typical of such common organisms are the following: Staphylococcus aureus; Staphylococcus epidermidis; Pseudomonas aeruginosa; and Serratia marcescens. A serious objection to bactericidal candidates is that they are highly active against many of these common organisms, but only mildly active against others. Naturally this represents a serious shortcoming.

In addition, of course, the candidate composition must have the requisite activity with relatively small concentrations of the active ingredient. Naturally, also, the candidate composition must be non-toxic when used externally.

As can be readily appreciated, the foregoing represent severe requirements which are extremely difficult to satisfy. Nonetheless, as can also be readily appreciated, there is a real need for compositions which satisfy all of these requirements.

Accordingly, it is a principal object of the present invention to provide bactericidal compositions.

It is an additional object of the present invention to bactericidal compositions which are inexpensive and have bactericidal activity against a wide variety of organisms, especially those commonly encountered.

An additional object of the present invention is to provide bactericidal compositions as aforesaid which are non-toxic.

Additional objects and advantages of the present invention will appear hereinafter.

SUMMARY OF THE INVENTION

In accordance with the present invention it has now been found that the foregoing objects and advantages can be readily obtained. The aqueous bactericidal composition of the present invention consists essentially of from 5 to 15 percent of an aliphatic monocarboxylic acid containing from 8 to 11 carbon atoms and the balance essentially a material selected from the group consisting of non-ionic detergents and anionic detergents.

It is a particularly surprising feature of the present invention that the monocarboxylic acid and the detergent exhibit a synergistic relationship and achieve a completely unexpected degree of bactericidal activity. For example, the monocarboxylic acids used herein are known to have bactericidal activity, see Canadian Patent No. 553,057; however, this activity is limited. Similarly, the detergents used herein are also known to have some bactericidal activity. However, one would not at all anticipate that the combination of the two would provide such remarkable bactericidal activity as is shown in accordance with the present invention. Thus, compositions of the present invention within (5) minutes killed 100 percent of the common bacteria Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Serratia marcescens. This is especially remarkable since the components separately do not at all show this level of activity and since a popular commercial preparation does not show this level of activity.

An important characteristic of the materials used in accordance with the present invention is that they have highly desirable aqueous solubility characteristics. Also, they may, in combination with the detergents, combine with and disrupt bacterial cell membranes. This is supported by the remarkable activity that the compositions of the present invention exhibit against a large number of organisms.

DETAILED DESCRIPTION

As indicated hereinabove, the aqueous bactericidal composition of the present invention contains from 5 to 15 percent by volume of an aliphatic monocarboxylic acid containing from 8 to 11 carbon atoms. Pelargonic acid is the preferred species, although, of course, others may readily be employed, for example, octanoic acid, decanoic acid, undecylic and mixtures thereof.

The acid is used in admixture with a non-ionic or anionic detergent. These are synthetic detergents which have a cleansing action like soap, but are not derived directly from fats and acids. They are surface active agents and have structurally unsymmetrical molecules containing both hydrophilic, or water soluble groups, and hydrophobic, or oil-soluble chains.

Thus, anionic detergents form negatively charged ions containing the oil-soluble portion of the molecule. The ionizable group is the hydrophilic portion. Typical anionic detergents which may be used include the sodium or potassium salts of organic sulfonates or sulfates and alkylaryl sulfonates.

Non-ionic detergents do not ionize but acquire hydrophilic character from an oxygenated side chain, usually polyoxyethylene. The oil-soluble part of the molecule may come, for example, from fatty acids, amides, alkylphenols or fatty alcohols. One can regulate the length of the polyoxyethylene chain and hence vary the melting, foaming, and detergent properties. Typical examples of non-ionic detergents include ethoxylated octyl phenol, tridecyl alcohol or tall oil.

Naturally, one may readily utilize mixtures of anionic detergents, or mixtures of non-ionic detergents or an anionic-nonionic detergent mixture. One may also employ emulsifiers or other additives in order to achieve a desired consistency or accentuate a particular property. Thus, for example, one may utilize lanolin.

The mixture of acid and detergent is then diluted with water, generally using at least about 25 percent by volume of the mixture and the balance water. The surprising bactericidal activity of these mixtures is particularly striking in view of the fact that dilute solutions may be employed.

It is a particularly surprising feature of the present invention that the acid-detergent combination exhibits a synergistic effect and attains bactericidal activity far greater than that which can be normally anticipated. This will be seen from a consideration of the data which is included in the present specification. One would not normally anticipate such remarkable properties as a 100 percent kill of the common organisms.

A particular advantage of the compositions of the present invention are their relatively low cost and easy availability. Furthermore, the components of the compositions of the present invention are known to be non-toxic when used externally, which is an important consideration. An additional advantage of the compositions of the present invention in normal use is that they operate near neutral, that is at a pH of from 6 to 8 and generally from 6.5 to 7.5. A further and significant advantage is their storage stability, even after prolonged storage.

Other compounds which have shown surprising bactericidal activity in combination with the detergents of the present invention include undecylenic acid (10-undecenoic acid) and 10-undecenoic acid ozonide.

The present invention and improvements resulting therefrom will be more readily understood from a consideration of the following illustrative examples.

EXAMPLE 1

This example describes the standard serial pour plate dilution technique which was used to determine the bactericidal activity. Four organisms were used in this study. A strain of coagulase positive Staphylococcus aureus; a strain of coagulase negative, mannitol negative Staphylococcus epidermidis; a strain of Pseudomonas aeruginosa; and a strain of Serratis marcescens. An inoculum was prepared for each bacterial strain by placing some of the bacteria from a colony into 10 ml. of Heart Infusion Broth and incubating at 37.degree. C. for 18 hours. After incubation, the number of bacteria per milliliter of inoculum was determined by 10-fold serial dilutions of the inoculum in Heart Infusion Broth. Specifically, 1 ml. of the inoculum was placed into 9.0 ml. of sterile broth in a test tube. This was mixed on a Vortex mixer and 1 ml. of this mixture (10.sup..sup.-1) was placed in 9.0 ml. of sterile broth in a second test tube and mixed (10.sup..sup.-2 dilution). This procedure was repeated (8) times so that the final test tube mixture contained a 10.sup..sup.-8 dilution of the original inoculum. Then 1.0 ml. of the 10.sup..sup.-5, 10.sup..sup.-6, 10.sup..sup.-7, and 10.sup..sup.-8 dilutions were placed in sterile Petri dishes to which 15 ml. of melted agar was added. This mixture was then rotated gently in the sterile Petri dish until it was mixed evenly, allowed to harden and placed in an incubator at 37.degree. C. for 24 hours. After this, the number of colony forming units of bacteria were counted on a colony counter and recorded. This number multiplied by the log-fold dilution, provides the accurate number of bacteria per milliliter in the original inoculant. The above procedure was carried out in each experiment for each bacteria used.

EXAMPLE II

In this example, the bacterial inoculum was added to Heart Infusion Broth and the amount of bacteria present after a (5) minute period determined. This was done in order to provide a control on the number of bacteria that should be theoretically present at (5) minutes after mixing the compounds with a known number of bacteria. The results are shown in Table I below.

TABLE I -- CONTROL ______________________________________ Staph. aureus No. of bacteria/ml. 0 min. -- 10,000,000 5 min. -- 14,300,000 Staph. epidermidis No. of bacteria/ml. 0 min. -- 10,000,000 5 min. -- 13,500,000 Pseud. aeruginosa No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 48,600,000 Serr. marcescens No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 25,600,000 ______________________________________

EXAMPLE III

The bactericidal activity of a particular composition was determined by testing the effect on a known number of bacteria within a (5 ) minute period. A known concentration of each compound was added to a known number of bacteria per milliliter and mixed on a Vortex mixer. After (5) minutes of incubating the bacteria with the compound, an aliquot of the mixture was serially diluted by the standard pour plate dilution technique of Example I. Subsequent aliquots of the serial dilutions were added to sterile Petri dishes to which melted agar was added, mixing was performed and the agar was allowed to harden. The hardened agar plates were incubated at 37.degree. C. for 24 hours and the number of colonies were counted on a colony counter after incubation. The number of colonies counted times the dilution factor represents the remaining number of bacteria per milliliter. The results are shown in Table II below. In this example, the composition employed was a 10 percent aqueous solution of pelargonic acid.

TABLE II ______________________________________ Staph. aureus No. of bacteria/ml. 0 min. -- 3,000,000 5 min. -- 0 Staph. epidermidis No. of bacteria/ml. 0 min. -- 4,000,000 5 min. -- 0 Pseud. aeruginosa No. of bacteria/ml. 0 min. -- 4,000,000 5 min. -- 400,000 Serr. marcescens No. of bacteria/ml. 0 min. -- 2,000,000 5 min. -- 100 ______________________________________

Thus, this compound was bactericidal in a 10 percent concentration to Staph. aureus and Staph. epidermidis, but only decreased the number of the others.

EXAMPLE IV

In a manner after Example III, the bactericidal activity of the following composition was determined.

______________________________________ Pelargonic Acid -- 10 parts by wt. Water -- 25 parts by wt. Nonionic detergent -- ethoxylated octyl phenol with 12 moles of ethylene oxide -- 90 parts by wt. ______________________________________

The composition was employed as above. The results are shown below.

TABLE III ______________________________________ Staph. auerus No. of bacteria/ml. 0 min. -- 3,000,000 5 min. -- 0 Staph. epidermidis No. of bacteria/ml. 0 min. -- 4,000,000 5 min. -- 0 Pseud. aeruginosa No. of bacteria/ml. 0 min. -- 4,000,000 5 min. -- 0 Serr. marcescens No. of bacteria/ml. 0 min. -- 2,000,000 5 min. -- 0 ______________________________________

Thus, this composition was bactericidal for all organisms tested.

EXAMPLE V

In a manner after Example III, the bactericidal activity of an anionic detergent base was determined, the base being similar to those used in commercial preparations. The detergent base had the following composition.

______________________________________ Modified ammonium alkyl sulfate -- 50 parts by wt. Emulsifier-mixture of fatty acid, mono-, di- and tri-glycerides -- 5 parts by wt. Water soluble lanolin (polyoxyethylene derivative) -- 1 part by wt. Water -- 41 parts by wt. Ammonium chloride -- 3 parts by wt. ______________________________________

The composition was applied in a 50 percent aqueous solution and in a concentration of 100 percent. The results are shown below.

TABLE IV -- 50% SOLUTION ______________________________________ Staph. aureus No. of bacteria/ml. 0 min. -- 10,000,000 5 min. -- 1,000,000 Staph. epidermidis No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 20,000,000 Pseud. aeruginosa No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 10,000,000 Serr. marcescens No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 10,000,000 ______________________________________

Thus, it can be seen that in a 50 percent concentration the anionic detergent base was virtually ineffective. The test was repeated in a concentration of 100 percent and the results are shown below.

TABLE V -- 100% SOLUTION ______________________________________ Staph. aureus No. of bacteria/ml. 0 min. -- 10,000,000 5 min. -- 100,000 Staph. epidermidis No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 200,000 Pseud. aeruginosa No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 5,000 Serr. marcescens No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 13,000 ______________________________________

Thus, even in a 100 percent concentration, the anionic detergent base simply decreased the number of organisms present, but clearly was not bactericidal.

EXAMPLE VI

In a manner after Example III, the bactericidal activity of the following composition was determined.

______________________________________ Pelargonic acid -- 11 grams Anionic detergent base of Example V -- 100 grams ______________________________________

The composition was diluted with an equal amount of water and the results are shown below.

TABLE VI ______________________________________ Staph. aureus No. of bacteria/ml. 0 min. -- 10,000,000 5 min. -- 0 Staph. epidermidis No. of bacteria/ml. 0 min. -- 10,000,000 5 min. -- 0 Pseud. aeruginosa No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 0 Serr. marcescens No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 0 ______________________________________ Thus, this composition was bactericidal for all organisms tested. This is particularly surprising since neither the pelargonic acid solution (Example III) nor the anionic detergent base (Example V) killed all organisms. The pelargonic acid solution killed some organisms, but simply decreased the number of others; while the anionic detergent base simply decreased the number of organisms present, even in 100% concentration. However, surprisingly, the present composition was dramatically bactericidal for all organisms even though lower concentrations of the ingredients were used and even though large numbers of organisms were present.

EXAMPLE VII

In a manner after Example III, the bactericidal activity of the following composition was determined.

______________________________________ Mixture of n-octanoic acid and n-decanoic acid -- 11 grams Anionic detergent base of Example V -- 100 grams ______________________________________

The composition was employed as above and the results are shown below.

TABLE VII ______________________________________ Staph. aureus No. of bacteria/ml. 0 min. -- 10,000,000 5 min. -- 0 Staph. epidermidis No. of bacteria/ml. 0 min. -- 10,000,000 5 min. -- 0 Pseud. aeruginosa No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 0 Serr. marcescens No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 0 ______________________________________

Thus, the composition was bactericidal for all organisms tested. In this example also, the dramatic bactericidal activity of the composition of the present invention was clearly apparent.

EXAMPLE VIII

In a manner after Example III, the bactericidal activity of the nonionic detergent used in Example IV was determined. The composition tested was a 100 percent concentration of ethoxylated octyl phenol with 12 moles of ethylene oxide. The results are shown below.

TABLE VIII ______________________________________ Staph. aureus No. of bacteria/ml. 0 min. -- 10,000,000 5 min. -- 300,000 Staph. epidermidis No. of bacteria/ml. 0 min. -- 10,000,000 5 min. -- 1,000,000 Pseud. aeruginosa No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 20,000 Serr. marcescens No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 7,000,000 ______________________________________

Thus, the nonionic detergent base, even in a 100 percent concentration, simply reduced the number of organisms present and was hardly effective against Serratia marcescens.

EXAMPLE IX

In a manner after Example III, the bactericidal activity of the commercial preparation PHISOHEX was determined in a 100 percent concentration. The results are shown below.

TABLE IX ______________________________________ Staph. aureus No. of bacteria/ml. 0 min. -- 10,000,000 5 min. -- 0 Staph. epidermidis No. of bacteria/ml. 0 min. -- 10,000,000 5 min. -- 0 Pseud. aeruginosa No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 20,000 Serr. marcescens No. of bacteria/ml. 0 min. -- 20,000,000 5 min. -- 200,000 ______________________________________

Thus, this composition was bactericidal to Staph. aureus and Staph. epidermidis, but simply reduced the number of organisms in Pseud. aeruginosa and Serr. marcescens. Hence, this commercial preparation was clearly not bactericidal for all organisms.

This invention may be embodied in other forms or carried out in other ways without departing from the spirit or essential characteristics thereof. The present embodiment is therefore to be considered as in all respects illustrative and not restrictive, the scope of the invention being indicated by the appended claims, and all changes which come within the meaning and range of equivalency are intended to be embraced therein.

Claims

1. An aqueous composition having synergistic bactericidal activity consisting essentially of from 5 to 15 percent of an aliphatic monocarboxylic acid containing from 8 to 11 carbon atoms selected from the group consisting of pelargonic acid, octanoic acid, decanoic acid and undecylic acid, balance a material selected from the group consisting of non-ionic detergents and anionic detergents, said non-ionic detergent being selected from the group consisting of ethoxylated alkylphenols and ethoxylated fatty alcohols, and said anionic detergent being selected from the group consisting of alkyl aryl sulfonates and alkyl sulfates, wherein said composition contains at least 25 percent of acid and detergent and

2. A composition according to claim 1 wherein said monocarboxylic acid is a

3. A composition according to claim 1 wherein a non-ionic detergent is

4. A composition according to claim 1 wherein an anionic detergent is

5. A composition according to claim 1 wherein said monocarboxylic acid is

6. A composition according to claim 1 having a pH of from 6 to 8.