US3193453A

US3193453A - Antibacterial compositions

Info

Publication number: US3193453A
Application number: US227584A
Authority: US
Inventors: Quinn Herbert
Original assignee: Procter and Gamble Co
Current assignee: Procter and Gamble Co
Priority date: 1962-10-01
Filing date: 1962-10-01
Publication date: 1965-07-06
Anticipated expiration: 1982-07-06

Description

United States Patent 0 ice 3,193,453 ANTTBACTEREAL CGWOSITIONS Herbert Quinn, ycamore Township, Ohio, assignor to The Procter & Gamble Company, Cincinnati, Ohio, a corporation of Ohio No Drawing. Filed Get. 1, i962, Ser. No. 227,584 1 Claim. (Cl. 1161-30) This invention concerns antibacterial compositions consisting of a mixture of antibacterial agents which exhibit 1 enhanced antibacterial activity when used in combination with each other. More specifically this invention relates to a mixture of one or more commonly used bisphenol antibacterial agents as described more fully herein in combination with certain imino-imidazolidines, the mixture exhibiting enhanced antibacterial activity and particularly when incorporated into a soap, or detergent product formulation.

In recent years there has been a markedly increased usage of soaps and detergent products containing antibacterial agents by housewives and other consumers. This is due principally to the increased awareness by the consumer of the need to maintain and insurehealthful living conditions. Many compounds have been suggested in past years for use as antibacterial agents in soaps, detergents, shampoos, and other surfactant based compositions; most of those compounds suggested, however, had some serious deficiencies which limited their utility. Such deficiencies were, for instance, ineffectiveness in soap solution, too great a toxicity, photosensitivity, and effective halogenated carbanilide's, halogenated bisphenols and the' halogenated salicylanilides have been disclosed. The synergism or enhanced activity provides a higher level of antibacterial effectiveness for an equal amount of anti bacterial agent used, or more important, it enables a manufacturer to use a lesser amount of antibacterial agents yet retain a relatively high degree of effectiveness, thereby enabling a less expensive product to be manufactured. This would be particularly helpful when the bisphenols are being used, as the discoloration of the soap caused by photosensitivity of this antibacterial agent 'is almost directly proportional to the amount of agent used, i.e., the higher the amount used, the greater the discoloration. It is significant to note that effective synergistic combinations of antibacterial agents or combinations which show enhanced activity are relatively rare and when such combinations are discovered, the synergism or enhancement is entirely unpredictable. It should be appreciated, therefore, that there is a need for still more effective antibacterial agents and combinations of agents having greater activity than has previously been known and which can be incorporated into soaps, detergent com- 3,193,453 Patented July 6, 1965 positions and other formulations without substantial lirnitations. I

It is therefore an object of this invention to provide antibacterial compositions having enhanced activity which possess a high level of antibacterial effectiveness.

It is a further object of this invention to provide antibacterial compositions which are effective in a soap or detergent product medium.

It is a still further object of this invention to provide antibacterial compositions which are economical and which do not have significant discoloration problems or toxicity problems.

Other objects and improvements will become apparent from the following description.

In accordance with this invention, it has been found that mixtures of (A) halogenated bisphenols and (B) substituted imino-imidazolidines, as hereinafter more fully described, exhibit enhanced antibacterial activity and particularly when incorporated into a fatty acid soap or synthetic anionic, nonionic, ampholytic or amph'oteric detergent composition at a ratio of (A) to (B) ranging from about 5:1 to about 1:5.

As used herein enhanced activity means antibacterial activity that is greater than would be expected if the compounds acted independently when used as the same total percentage level.

The substituted bisphenols used in the mixtures described herein have the general formula:

OH OH Xll X where X is a halogen and n is an integer from 1 to 3 inclusive, and R is selected from the group consisting of alkylene radicals having from 1 to 4 carbon atoms and divalent sulfur.

Halogenated bisphenols which find utility in this invention are, for example, those disclosed in US. Patent 2,535,077, K-unz et al., and include bis-(Z-hydroxy- 3,5,6-trichloro phenyl)methane and bis-(2-hydroxy-3,5- dichloro phenyl)methane. Other suitable bisphenols include, for example, bis-(2-hydroxy-3,5,6-trichlorophenyl)- sulfide and bis-(2-hydroxy-3,S-dichlorophenyl)-sulfide.

The substituted imino-imidazolidine compounds used in the mixtures of this invention have the general formula:

wherein R is an alkyl radical having from 12 to about 18 carbon atoms and R is selected from the group consisting of hydrogen, and .alkyl radicals .having from 1 to 6 carbon atoms.

These compounds are disclosed in US. Patent 2,999,-

047, Model et 'al. Those compounds which find particular usefulness are, for example, l-dodecyl-Z-imino-imidazolidine hydrochloride, 1-tetradecyl-2-imino-imidazolidine hydrochloride, 1-dodecyl-3-butyl-2-iminoimidazolir 3 dine hydrochloride, l:dodecyl-E.-cyclohexyl-2-iminoimidazolidine hydrochloride, l-tetradecyl-3-acetic acid-2- iminoimidazol'idine hydrochloride, and 1-dodecyl-3-acetic acid-Z-iminoimidazolidine hydrochloride.

The following combinations of antibacterial agents are illustrative of the mixtures of this invention possessing enhancedactivity but should not be considered as limiting the scope of the invention.

Ratio of parts Cloth protection test Total Anti- Bacterial bacterial Colonies Sur- Compound Agent (s) as Ratio viving Per Percent in Sq. In. Cloth, BSD 1 S. aureus .25 1, 500 IMD .05 1,917 1 1 9 I v 1 B- G''11 1 171 1,792 o. rMD+G-n 1,408 1)., Detergent (Control) 2,192 E. Water wash 2,142

EXAMPLE II In this example the enhancedactivity of the combinations of thisinvention is'shown by means of the Standard Tube Dilution Test, which consists essentially of preparing serial dilutions of the antibacterial composi- 1-dodecyl-2-iinino-imidazolidine hydrochloride 3 Bis (2-hydroxy-3, l,6-trichlorophenyl)methane l V 1-tetradecyl-2-imino-imidazolidine hydrochloride 4 Bis(2-l1ydroxy-3,S-dichlorophenyl) sulfide 1 l-dodecyl-imirio-imidazolidine hydrochloride 1 Bis(2-hydroxy-3,S-chlorophenyl) methane 1 l-tetradecyl-Z-imino-imidazolidine hydrochloride 2 Bis(2-hydroxy 3,5,6atrichlorophenyl) sulfide 3 1-tetradecyl-Z-imino-irhidazolidine hydrochloride ,3 Bis(2-hydroxy-3,S-dichlorophenyl) sulfide 1 1-tetradecyl-3-butyl-2 imino-imidazolildine hydrochloride 5 Bis(Z-hydroxy-3,5 chlorophenyl methane 1- l-tetradecyl-3-acetic acid-Z-imino-imidazolidine hydrochloride 1 Bis(2-hydroxy-3,5,6rtrichlorophenyl) sulfide 5 l-tetradecyl-3-butyl Z-imino-imidazolidine 4. 2 Bis(2-hydroxy-3,5,6-trichlorophenyl) sulfide 1 l-octadecyl-2-imino-imidazolidine 1 Bis-(2-hydroxy-3,S-dichlorophenyl) sulfide. 1

It has been found that the above listed combinations and similar variations thereof possess enhanced antibac terial properties whereby a lasting antibacterial efiect is obtained particularly when they .are usedrin fatty acid 7 soap and anionic, nonionic, ampholytic, and 'amphoteric V synthetic detergent compositions and other products where an antibacterial action is desired. This enhanced activity can be more readily seen by reference to the following examples based on representatives of the above combinations.

EXAMPLE 1 tions to be tested 'in a FDA broth medium, inoculating with the chosen test organism and observing the weakest sentthe compounds indicated:

1MB 1-dodecyl-Z-iminoirnidazolidine hydrochloride G-11bis(2-hydroxy-3,5,6-trichlorophenyl) methane to dry and then they are planted in an agar medium Petri plate with the inoculated surface up and anfoverlay of nutrient is added over the fabric. The Petri plates are then incubated at 37 C. for 48 hours and thereafter bacterial counts are taken by means of a low-power dis secting microscope; The relative ability of a' treated" figure represents'anaverageof the organisms found on six replicate cloth swatches. H V In this example the following letter abbreviations represent'the compounds indicated. i

IMD1dodecyl-2imnioimidazolidine hydrochloride G-l1bis(2-hydroxy-3,5,6-trichlorophenyl) methane V Bacteriostatic breakpoints Compound Ratio Totalppm.

S. aureus 1. IMD r 0.9 2. G41 0.11 3. IMD/G-11 1:1 0.14 (EA) Expressed as p.p.m. total quantity of antibacterial agent required to inhibit; growth of S. aureus organism.

(EA) indicates enhanced activity.

the combinations shown. r

.Relatively small amounts of the enhanced antibacterial fmixtures of the present invention are sufficient to render soap or detergent compositions antibacterially active.

.The soap or detergent composition can be in liquid, solid,

. flake, granular 'or other similar form. JA soap or detergent composition is termed antibacterial if it is effective in I killing or inhibiting the growth of'the' Staphylococcus aureus organism, whether or not it happens to be effective against any other type of bacteria. V

Because of the enhanced activity of the mixtures of compounds of the present invention, it willbe appreciated that smaller amounts than usual with conventional antibacterial agents can be incorporated into the soap or detergent compositions and still achieve good antibacterial effectiveness. Amounts as low as .l% of the enhanced mixtures described herein have proved satisfactory; however, it is preferred to use amounts of the mixtures ranging from 1% to 2% by total weight of the soap bar or detergent composition. The upper limit of the amount of agent to be used is determined by practical and economic considerations and is usually about 5%. The ratios of the agents listed under (A) and (B) supra can range from about 5:1 to about 1:5 with the preferred ratio being about 1: 1.

Generally speaking, an increase in concentration of the mixture having enhanced activity increases the antibacterial effectiveness of the soap or detergent products. However, it is apparent that the cost of the agent in the soap, detergent composition, or other surfactant formulation mitigates against the use of an excessive amount. Additionally, if too large an amount is incorporated into the soap or detergent composition, the detergent properties of the product may be lessened.

The preferred antibacterial combinations which exhibit the most enhanced activity for use in this invention include bis-(2-hydroxy-3,S,6-trichlorophenyl) methane in combination with 1-dodecyl-2-iminoimidazolidine hydrochloride, and bis-(2-hydroxy-3,5,6-trichlorophenyl) sulfide in combination with 1-dodecyl-2-iminoimidazolidine hydrochloride, all at a 1:1 ratio.

The term soap as used herein is meant to designate alkali metal soaps such as sodium and potassium salts of the higher fatty acids of naturally occurring plant or ani mal esters (e.g., palm oil, coconut oil, babassu oil, soybean oil, castor oil, tallow, whale and fish oils, grease and lard, and mixtures thereof). Sodium and potassium soaps can be made by direct saponification of the fats and the oils or by the neutralization of the free fatty acids which are prepared in a separate manufacturing process.

The anionic synthetic detergent agent which can be employed with this invention is generally defined as a water soluble salt of an organic sulfuric reaction product having as its molecular structure an alkyl group containing from about 8 to about 22 carbon atoms and a radical selected from the group consisting of sulfonic acid and sulfuric acid ester radicals.

Important examples of the synthetics of this group which can be benefited through the incorporation therein of the mixtures of this invention, are the sodium or potassium alkyl sulfates, especially those derived by sulfation or" higher alcohols produced by reduction of glycerides of tallow or coconut oil, sodium or potassium alkyl benzene sulfonates, especially those of the types described in U.S. Letters Patent 2,220,099, granted November 5, 1940, and 2,477,383, granted July 26, 1949, in which the alkyl group contains from about 9' to about 15 carbon atoms; sodium or potassium alkyl glyceryl ether sulfonates, especially those others in which the alkyl group is derived from the higher alcohols from tallow or coconut oil; sodium coconut oil fatty acid monoglyceride sulfates and sulfonates, sodium salts of sulfuric acid esters of the reaction product of one mole of a higher fatty alcohol (e.g., tallow or coconut oil alcohols) and about three moles of ethylene oxide, and others known in the art, a number being specifically set forth in Byerly, U.S. Letters Patent 2,486,921, granted November 1, 1949, and Strain,

U.S. Letters Patent 2,486,922, granted November 1, 1949.

Additional anionic surface active sulfonates and sulfates which can be employed in this invention are the sulfated and sulfonated alkyl acid amides such as Igepon T (C1I7H33CON(CH3)CH2CH2SO3N3.), the sulfated and sulfonated esters such as Igepon AP (RCOOCH CH SO Na) Where R is an alkyl radical containing from 11 to 17 carbon atoms) sodium salt of the bisulfate of a dialkyl dicarboxylate, sodium salt of the sulfonic acid derivative of a dialkyl dicarboxylate, sodium sulfosuccinic esters such as NaOOCCH CH(SO Na) CONHC H and the like.

A minor amount, totaling about 2% of a 1:1 mixture of bis-(2-hydroxy-3,5,6-trichlorophenyl) methane and 1- dodecyl-Z-imino-imidazolidine hydrochloride for example, renders a composition containing any of the above detergents or mixtures thereof, antibacterially active against the common organisms found on the skin.

The nonionic synthetic organic detergents which have utility in the practice of this invention may be broadly defined as compounds produced by the condensation of alkylene oxide groups (hydrophilic in nature) with an organic hydrophobic compound, which may be aliphatic or alkyl aromatic in nature. As those skilled in the art are well aware, the length of the hydrophilic or polyoxyalkylene radical required for condensation with any particular hydrophobic group can be readily adjusted to yield a water-soluble compound having the desired degree of balance between hydrophilic and hydrophobic elements.

For example, a well known class of nonionics is made available on the market under the trade name of Pluronic. These compounds are formed by condensing ethylene oxide with a hydrophobic base formed by the condensation of propylene oxide with propylene glycol. The hydrophobic portion of the molecule, of course, exhibits water insolubility. Its molecular weight is of the order of 1500 to 1800. The addition of polyoxyethylene radicals to this hydrophobic portion tends to increase the water solubility of the molecule as a whole. Liquid prodnets are obtained up to the point where polyoxyethylene content is about 50% of the total Weight of the condensation product.

Suitable nonionics also include the polyethylene oxid condensates or alkyl phenols, e.g., the condensation products of alkyl phenols having from 6 to 12 carbon atoms, either straight chain or branch chain, in the alkyl group with ethylene oxide in amounts equal to 10 to 25 moles of ethylene oxide per mole of alkyl phenol. The alkyl substituent in such compounds may be derive from polymerized propylene, diisobutylene, octane, or nonane, for example.

Other suitable nonionics may be derived by the condensation of ethylene oxide with the product resulting from the reaction of propylene oxide and ethylene di amine. Here again, a series of compounds may be produced, depending on the desired balance between hydrophobic and hydrophilic elements. For example, compounds (molecular weight from about 5,000 to about 11,000) of about 40% to polyoxyethylene content and resulting from the reaction of ethylene oxide groups with a hydrophobic base constituted of the reaction product of ethylene diamine and excess propylene oxide, said base having a molecular weight of the order of 2500 to 3000, are satisfactory.

Further satisfactory nonionics includethe condensation product of aliphatic alcohols having from 8 to 18 carbon atoms, either straight chain or branch chain, with ethylene oxlde, an example being a coconut alcohol ethylene oxide condensate having from 10 to 30 moles of ethylene oxide per mole of coconut alcohol, the coconut alcohol fraction having from 10 to 14 carbon atoms.

The ampholytic surface-active detergents which can be used in the practice of this invention have the general formula RZXM where R is an aliphatic hydrophobic group containing from about 8 to about 18 carbons, X is an anion selected from the group consisting of sulfonate, sulfate and carboxy radicals, Z is an intermediate group jointed to R by a member of the group consisting of ether, polyether, ester, amide and amine linkages, and M is a cation to neutralize the charge of the anion. Classification according to whether the detergent has an intermediate linkage or not is used in Surface Active Agents and Detergents, by A. M. Schwartz, J. W. Perry, and I. Berch, Interscience Publishers, New York, 1958, vol. II.

Examples of ampholytic compounds are disodium lauryl beta-iminodipropionate, dipotassium lauryl beta-iminodipropionate and alkyl beta-iminopropionate, where the alkyl group is 'derived from the middle cut or coconut alcohol or fatty acid.

Other detergent compounds which can be used in th scribed in US. patent application No. 163,042 and can be prepared in the manner disclosed in US. Patent 2,-

129,264 and German Patent 1,018,421. Specific examples are 3-(N,N-dimethyl-Nahexadecyl ammonio)-2-hydroxy propane-1 -sulfonate,' .3- (N,N-dimethyl-N-alkyl ammonio Z-hydroxypropane-l-sulfonate, the alkyl group being derived fromtaliow alcohol, 3-(N,N-dimethyl-N-dodecylammonio)-propane1-sulfonate, and 3-(N,N diethyl-N- hexadecyl ammonio) propane-I-sulfonate.

. The enhanced mixtures of this invention have been found to increase the antibacterial activity of soap and non-soap synthetic detergent compositions in bar, liquid, flake, granular and other forms and can be incorporated into the soap or detergent composition by any suitable method preferably which yields as a result a uniform dis tribution of agents throughout the whole mass.

Regular use of a Camay or Ivorytype soap bar conta'ming 1.5% of the mixtures of this invention. possessing enhanced activity, e.g., 1% bis(2-hydroxy-3,5,6-tri. chlorophenyl) methane plus .5 l-dodecyl-Z-iminoimidaz-olidine hydrochloride results in substantial reductions in the bacterial population of the skin and thereby markedly reduces body odor attributable to the bacterial deg- 20.5% potassium alkyl sulfate (alkyl group derived from the middle cut'of alcohols obtained by the catalytic reduction of coconut oil) p 8.0% sodium alkyl'glyceryl ether sulfonate (alkyl group derived from the middle cut of alcohols obtained'by catalytic reduction of coconut oil) 33.81% sodium soap of 20:80 coconut:tallow fatty acids 7 17.07% magnesium soap of 20:80 coconutztallow fatty acids 5.81% inorganic salts .75% bis(2-hydroxy-3,'5,6-trichlorophenyl) methane 50% 1-tetradecyl-2-iminoimidazolidine ,hydrochlorid 8.0% moisture i Balance miscellaneous a .This bar exhibits'goododor reducing properties and re duces the numbers of bacteria on the skin and does not discolor significantly.

A granular built synthetic detergent compositionhaving the following formulation can beprepared by spray drying and the antibacterial agents of this invention can be incorporated therein. This composition imparts considerable antibacterial activity to. fabrics washed in the solution.

17.5% sodium alkyl benzene sulfonate (the alkyl radical averaging about 12 carbon atoms and being derived from polypropylene),

. 47.9% sodium tripolyphos'phate 13.3% sodium sulfate i 7.0% silicate solids V .75 bis(Z-hydroxy-3,5-dichlorophenyl) methane .75% 1rtetradecyl-2-in1inoimidazolicline Balance water .and miscellaneous The invention has been described above in conjunction with various illustrative examples of antibacterial compositions, toiletand laundry detergents. It will be obvious to those skilled in the art, however, that the antibacterial mixtures can also be beneficially employed in such products as shampoos, antiseptic ointment, foot powders, and

the like.

What is claimed is: r 7 An antibacterial composition comprising a combination of (A) bis(2-hydroxy-3,Sfi-trichlorOphenyl) methane and (B) 1-dodecyl-2 iminoimidazolidine hydrochloride, the proportions by weight'of (A) and (B) being about 1:1,

said combination displaying'a synergistic antibacterial ac tion When used with water from a medium in which the concentration of the said combination ranges from about 0.1% to about 0.5% by weight.

References Cited by the Examiner UNITED STATES PATENTS JULIAN s. LEvrrT, Primary Examiner.

J. GREENWALD, Examiner. V