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Publication numberUS3485919 A
Publication typeGrant
Publication dateDec 23, 1969
Filing dateSep 5, 1963
Priority dateSep 5, 1963
Publication numberUS 3485919 A, US 3485919A, US-A-3485919, US3485919 A, US3485919A
InventorsJohn H Markgraf, Herbert Quinn
Original AssigneeProcter & Gamble
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Antibacterial composition
US 3485919 A
Images(8)
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Description  (OCR text may contain errors)

United States Patent 3,485,919 ANTIBACTERIAL COMPOSITION John H. Markgraf, Williamstown, Mass., and Herbert Quinn, Sycamore Township, Ohio, assignors to The Procter & Gamble Company, Cincinnati, Ohio, a corporation of Ohio No Drawing. Filed Sept. 5, 1963, Ser. No. 306,676 Int. Cl. A611 13/00 U.S. Cl. 424322 1 Claim ABSTRACT OF THE DISCLOSURE Mixtures of commonly-used antibacterial agents together with para-substituted alkyl phenol enhancers. Antibacterial agents are 3-trifluoromethyl-4,4-dichlorocarbanilide, 3,4,4'-trichlorocarbanilide or bis(2-hydroxy- 3,5,6-trichlorophenyl)methane. Enhancers are p-tetrapropylene phenol or p-dodecyl sulfonyl phenol.

This invention relates to novel antibacterial compositions comprising an antibacterial agent in admixture with an organic compound which enhances its antibacterial activity. More specifically this invention relates to a mixture of one or more commonly used anti-bacterial agents as described more fully herein and certain paraalkyl phenols and para-alkyl sulfonyl phenols, also described more fully herein, which phenols enhance the activity of the antibacteria agents, particularly when the mixture is incorporated into a soap, or detergent product formulation.

In recent years a major cause of infections in hospitals, clinics, and other places of a medical nature, has been the Staphylococcus organisms (particularly the various pathogenic strains of Staphylococcus aureus) which are residual in the hospital atmosphere, on the furnishings, and on the bedding and other linens used by patients. Many investigators believe the reason these organisms are extant is due primarilly to inadequate disinfecting procedures. It was once believed that with the discovery of antibiotics which could control the Staphylococcus organisms, the necessity of practicing stringent disinfecting procedures with chemical antibacterial agents would be eliminated. Since there are now a variety of Staphylococcus organisms resistant to the action of the common antibiotics and the number is constantly increasing, the disregard of normal chemical disinfecting procedures allows the organism to multiply unrestricted; consequently, it has been found necessary to return to the stringent and continuous disinfecting procedures used before the advent of antibiotics to obtain adequate organism control.

A method which has been used to obtain a measure of control over the Staphylococcus and other organisms on bed linens, blankets, and other fabrics used in hospitals and also in the home has been to rinse them in solutions containing germicidal agents, or wash them in soap or detergent solutions containing germicidal agents. Agents which have been incorporated into soap and detergent compositions are, for example, the substituted bisphenols, the substituted carbanilides, the substituted salicylanilides, and others. These agents have also been incorporated into hand soap and detergent bars for use 3,485,919 Patented Dec. 23, 1969 by doctors and other consumers to reduce the level of bacteria on the hands and body.

Although these compounds provide good antibacterial control when incorporated into bar and other types of soap and detergent compositions, the compounds are quite expensive when compared to the other ingredients of the composition. Another deficiency, at least with respect to the bisphenols, is their photosensitivity. When exposed to sunlight (ultraviolet light) the bisphenols discolor the soap or detergent matrix they are incorporated in, making an unsightly product. In addition, too high a level of antibacterial agent'in a soap or detergent product creates formulation problems and it is difficult to make a product acceptable to the consumer.

Some of these problems, particularly the cost and formulation problems, have been alleviated somewhat by the discovery that certain binary combinations of antibacterial agents exhibit synergism when admixed and incorporated into soap and detergent formulations. Synergistic combinations of antibacterial agents such as the halogenated bisphenols and halogenated carbanilides, halogenated bisphenols and the halogenated salicylanilides, have been disclosed. The synergism or enhanced activity of these combinations provides a higher level of antibacterial effectiveness for the same total amount of antibacterial agent. More important, it enables a manufacturer to use a lesser total amount of antibacterial agent while maintaining the desired high degree of effectiveness, thereby reducing the cost of the product. When the bisphenols are used, the reduced quantity of antibacterial agent permitted is particularly beneficial as the discoloration of the soap or detergent composition caused by the photosensitivity of these compounds is almost directly proportional to the amount used, i.e., the greater the amount used, the greater the discoloration. It is significant to note that effective synergistic combinations of antibacterial agents or combinations of compounds which show enhanced activity are relatively rare and such activity is entirely unpredicable. It can 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 attained and which can be incorporated into soaps, detergent compositions and other formulations without substantial limitations.

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

It is a further object of this object of this invention to provide antibacterial compositions exhibiting enhanced activity which are effective in a soap or detergent product medium and which impart antibacterial properties to fabrics and linens treated in aqueous solutions of them.

It is a still further object of this invention to provide anti-bacterial compositions which are economical. Other objects and improvements will become apparent from the following description.

In accordance with this invention, it has been found that certain para-alkyl and/ or para-alkyl sulfonyl phenols when admixed with an antibacterial agent selected from the group consisting of substituted bisphenols, substituted carbanilides, substituted salicylanilides, dibenziodolium salts, dibenzoxiodinium salts, phenyl mercuric salts, trialkyltin salts, triphenyltin salts, triphenylbismuth and salts thereof, other organometallic compounds, neomycin and derivatives, and others as more fully described hereinafter, enhance the antibacterial activity of the antibacterial agents or mixtures thereof when in aqueous solution or when incorporated into a soap or detergent composition at low levels of concentration.

The para-alkyl phenols and para-alkyl sulfonyl phenols described herein will be referred to as the enhancers or enhancing agents while the antibacterial agents will be referred to as the primary antibacterial agents or compounds.

The ratio of enhancing agent to primary antibacterial agent can range from about 1:1 to about 3000:1.

Unless otherwise indicated, the term alkyl phenol as used hereafter will refer to para-alkyl phenol and para-alkyl sulfonyl phenol compounds. The alkyl phenols used as enhancers in the practice of this invention have the general structural formula:

(IHI

where R is a member selected from the group consisting of alkyl and alkyl sulfonyl radicals containing from 9 to about 12 carbon atoms, X is a halogen atom and n is an integer of from to 4.

It has surprisngly been found that only alkyl phenols having alkyl substituents of certain critical chain lengths enhance the activity of the primary antibacterial agents.

The alkyl radical must contain from 9 to about 12 carbon atoms and can be either straight or branched chain. The phenol moiety can be substituted with as many as 4 halogen atoms, preferably chlorine atoms, however, a halogen substituent is not essential. Alkyl phenol compounds which find utility in the practice of this invention are, for example, p-nonyl, phenol, 2,6-dichloro-p-nonyl phenol, 2-chloro-p-nonyl phenol, 2-chloro-p-nonyl sulfonyl phenol, 2,5,6-trichloro-p-nonyl phenol, tetrachlorop-nonyl phenol, p-decyl phenol, 2-chloro-p-undecyl phenol, ptetrapropylene phenol the tetrapropylene radical being derived from polymerized propylene and averaging about 12 carbon atoms, p-dodecyl (straight chain) sulfonyl phenol, 2,6-dichloro-p-tetrapropylene phenol, -bromo-pdodecyl phenol, and S-chloro-p-dodecyl sulfonyl phenol. Preferred alkyl phenols for use in the compositions of this invention include p-dodecyl phenol and p-dodecyl sulfonyl phenol. These compounds can be prepared by alkylating the phenol compound at the para position and by methods described by Reed in U.S. Patent 2,391,798, granted Dec. 5, 1945; by Buc in U.S. Patent 2,104,412, granted Jan. 4, 1938, and Olin, U.S. Patent 2,107,060, granted Feb. 1, 1938.

Most of the above described non-halogen substituted compounds are commercially available on a large scale and are relatively inexpensive. The non-halogen substituted alkyl phenols are commonly used in the preparation of nonionic surfactants, i.e., the condensation products of alkyl phenols with ethylene oxide. The alkyl phenols, either halogenated or non-halogenated, have relatively poor antibacterial activity but when they are used in conjunction with the primary antibacterial agents described herein, they enhance the antibacterial activity of the primary agents. Since the alkyl phenols are much less expensive than the primary antibacterial agents described herein, and act to enhance the antibacterial activity of the primary agents when used in conjunction therewith, an antibacterial product can be produced containing the alkyl phenol in admixture with the primary antibacterial agent in which the quantity of expensive primary agent can be greatly reduced yet having the same overall antibacterial activity as a product containing only the primary agent at a higher level. Thus a much less expensive product can be produced.

Although it has surprisingly been found that the alkyl phenols described herein enhance the activity of most commonly used antibacterial agents, there are a few primary antibacterial agents which exhibit outstanding activity when used in conjunction therewith. Several preferred primary antibacterial agents for the purpose of this invention are set forth in the following disclosures.

Substituted carbanilides which exhibit enhanced activity when used in conjunction there with the alkyl phenols in the compositions of this invention and which are especially preferred primary antibacterial agents have the general formula:

wherein Y Y and Y are each selected from the group consisting of hydrogen, halogen, and trifluoromethyl, X is selected from the group consisting of halogen, trifluoromethyl, and ethoxy, and X is selected from the group consisting of hydrogen and halogen.

Especially preferred halogenated carbanilides include, for example, 3,4,4-trichlorocarbanilide, 3,3',4-trichlorocarbanilide, 3-trifluoromethyl 3,4 dichlorocarbanilide, 3 trifluoromethyl 4,4 dichlorocarbanilide, and 3- bromo-3,4-dichlorocarbanilide. These and other operable halogenated carbanilide compounds are fully described in U.S. Letters Patents 2,475,874, Schetty et al. granted May 15, 1956, and 2,846,398, Beaver et al., granted Aug. 5, 1958. These patents further disclose methods of preparation.

Antibacterial salicylanilide compounds which are enhanced in activity when used in conjunction with the alkyl phenols in the compositions of this invention have the general formula:

Y1 OH 0 where X is selected from the group consisting of hydrogen, trifluoromethyl, and halogen, X is selected from the group consisting of halogen and trifiuoromethyl, and Y Y Y and Y, are each selected from the group consisting of hydrogen, halogen, and trifluoromethyl.

Examples of preferred halogenated salicylanilide compounds which show enhanced activity when used in conjunction with the alkyl phenols in the compositions of this invention include, 3,5,4-tribromosalicylanilide, 5,4- dichlorosalicylanilide, 5 bromosalicyl 3,4 di(trifiuoromethyl) anilide, and 5' chlorosalicyl 3 trifiuoromethyl 4-chloroanilide. Other halogenated salicylanilides which come within the general formula above and display enhanced activity in the compositions of this invention are disclosed by Bindler and Model in U.S. Patent 2,703,352, granted Mar. 1, 1955. This patent further discloses a method for their preparation.

The substituted bisphenols which can be used as the primary antibacterial agent in the compositions of this invention have the general formula:

OH OH wherein X is a halogen and n is a positive integer of from 1 to 3 inclusive, and R is selected from the group 5 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 by Kunz et al. in U.S. Patent 2,535,077, granted Dec. 26, 1950, and Kunz et al. in US. Patent 2,353,735, granted July 18, 1944. Preferred compounds of this class include bis(2- hydroxy-3,5,6 trichlorophenyl) sulfide; bis(2-hydroxy- 3,4-dichlorophenyl) methane.

Still other primary antibacterial agents the antibacterial activity of which is enhanced by the presence of the alkyl phenols described herein are those having the general structural formula:

R fl GYD I Wherein R is selected from the group consisting of oxygen, sulfur, and (CH and m is an integer of from to 3; wherein Y is a radical selected from the group consisting of halogen, nitro, alkyl radicals containing up to 3 carbon atoms, halogen substituted alkyl radicals containing up to 3 carbon atoms, amino, and sulfamyl, and n is an integer of from 0 to 2, and wherein X is selected from the group consisting of organic and inorganic anions.

Specific examples of operable compounds of this class are bis(dibenziodolium) sulfate, 2,4 dichloro-di benziodolium sulfate, bis(3,7 dichlorodibenziodolium) sulfate, dibenziodolium lactate, bis[3,7-di(trifluoromethyl) dibenz iodolium] iodide, bis(3 chlorodibenziodolium) sulfate, bis(2,4 dichlorodibenziodolium) sulfate, and bis(2 chlorodibenziodolium) sulfate; also, bis[dibenz (b,e) (1,4) oxiodinium] sulfate, 3 chlorodibenz(b,e) (1,4) oxiodinium chloride, 3,7 dimethyldibenz(b,e) (1,4) oxiodinium chloride, and bis[3,7 dichlorodibenz (b,e) (1,4) oxiodinium] sulfate.

Suitable phenyl mercuric compounds can be used in the compositions of this invention as the primary antibacteria agent having the general formula:

wherein X is selected from the group consisting of N0 Cl, OH, OCOCH OCOCH CH and oleate. Specific examples are phenyl mercuric nitrate, phenyl mercuric chloride, phenyl mercuric acetate, and phenyl mercuric propionate.

Other organo-metallic compounds which exhibit enhanced antibacterial activity when used in the compositions of this invention include trialkyltin salts where the alkyl group ranges from 3 to 5 carbon atoms. The salt forming anion of these compounds can be any acid moiety. Included in the group are tripropyltin acetate, tripropyltin chloride, triisopropyltin resinate, tributyltin methacrylate, tributyltin phthalimide, tributyltin iodide, bis(tributyltin) oxide, triamyltin chloride, and triamyltin acetate. Still other operable organo-metallic compounds include triphenyltin chloride, bis(triphenyltin) oxide, triphenyltin acetate, triphenylbismuth dichloride, and triphenylbismuth.

Antibiotics such as neomycin and neomycin derivatives such as neomycin sulfate, neomycin palmitate, N-poly- (l-naphthylmethylene) neomycin, and neomycin B cupric undecenoate complex also exhibit enhanced activity when used in combination with the alkyl phenol enhancers in the compositions of this invention, Neomycin and deriva- 6 tives are described in the book Neomycin S. A. Waksman, Rutgers University Press, 1953.

The following combinations of primary antibacterial agents and alkyl phenols are illustrative of combinations which display enhanced activity in the practice of this invention.

Parts by weight p-Nonyl phenol 3 Bis(2-hydroxy-3,5,6-trichlorophenyl) methane 1 p-Nonyl phenol 1O 3,4,4-trichlorocarbanilide 1 2,6-dichloro-p-dodecyl phenol 2 Bis(2-hydroxy-3,5,6-trichlorophenyl) methane 1 2,6-dichloro-p-dodecyl phenol M 16 3,4,S-tribromosalicylanilide l 2-chloro-p-nonyl phenol 1O Phenyl mercuric acetate 1 p-Dodecyl sufonyl phenol 5 Neomycin sulfate 1 Tetrachloro-p-nonyl phenol 4 Bis-(dibenziodolium) sulfate 3 p-Nonyl phenol 6 3,7-dibromodibenz(b,e) (1,4) oxiodinium chloride 1 Tetrachloro-p-dodecyl phenol 2 Tri-n-propyltin acetate 1 p-Decyl sulfonyl phenol 12 3-trifluoromethyl-4,4'-dichlorocarbanilide 1 2-chloro-p-undecyl phenol 3 Triphenylbismuth dichloride 1 2,6-dichloro-p-nonyl phenol 4 4,5-dibromosalicylanilide 1 p-Dodecyl (tetrapropylene) phenol 2 Bis(dibenziodolium) sulfate 1 2,6-dichloro-p-undecyl phenol 1O 3-trifiuoromethyl-4,4-dibromocarbanilide 1 p-Nonyl sulfonyl phenol 7 3,4,5-tribromosalicylanilide 1 S-chloro-p-nonyl sulfonyl phenol 4 Neomycin 1 2,6-dichloro-p-undecyl phenol 2 Phenyl mercuric oleate 1 Tetrachloro-p-nonyl phenol 3 3,4,3,4-tetrachlorosalicylanilide 2 2-chloro-p-nonyl phenol 6 Neomycin sulfate 1 2,6-dibromo-p-dodecyl sulfonyl phenol 5 Tributyltin chloride 1 2,6-dichloro-p-dodecyl phenol 8 Bis(2-hydroxy-3,5-dichlorophenyl) sulfide 1 Each of the foregoing combinations is dissolved to yield a total concentration of C These compositions containing the combination of enhancer at concentration C and primary antibacterial at concentration C possess greater antibacterial activity than do solutions of the primary antibacterial agents at concentration C which is greater than C Thus much less of the expensive primary antibacterial agent can be used without loss of the desired activity. The enhanced activity is maintained when the compositions are used in soap and non-soap anionic, nonionic, ampholytic and amphoteric synthetic detergent compositions. While the enhanced antibacterial activity for the compositions of this invention can be displayed in simple aqueous solutions, their greatest utility is manifested when the combination of primary antibacterial agent and enhancer is designed for the treatment of linens, bedding and other fabrics, or for the cleansing of the human body. The enhanced activity can be seen from the following examples wherein representative combinations of primary antibacterial agents and enhancers are tested.

A convenient and meaningful method of measuring the antibacterial effectiveness of the compositions of this invention is by means of the Cloth Protection Test,

cates greater antibacterial effectiveness. Each figure represents the average of the organisms found on at least 6 replicate cloth swatches.

TABLE I.-EFFECT ()I LEN (llli ()1 ALKYL GRO U1 ALKYL lllENOLS ON THE POWER TO ENHANCE ANTIBAUTE lilAL ACTlVlTY O1 1 RIMARY ANTIBACTERIAL (JUMBO UNDS Colonies of 8. names Surviving ler Sq. inch of C 1.75% alkyl 1.75% alkyl 1.75% alkyl 0.05% 0.05% phenol plus phenol plus Compositions phenol 'IFC G-ll 05% TFO 05% (3-11 1, 060 3. p-n-Propyl phenol NC 1 1, 930 2, 330 4 p-Crotyl phenol NC 1,950 2, 540 5 p-t-Amyl phenol r. NC 2,090 2,430 6 p-Oetyl phenol NC 1,570 2, 210 7 p-Nonyl phenol. N C 170 240 8. 2,6-(lichlo1'op-nonylphenol" NC 260 440 9. p-Tetrapropylene phenol N C 1 40 10. p-Dodecyl sulfonylphenoL NC 1 11. p-Ilexadecyl phenol NO 2,750

1 NC 0i' ne means no significant control over the organism was obtained. indicates composition was not tested. Values above 1,900=No significant control.

H. Quinn, Applied Microbiology (January 1962). Briefly, the test consists of washing uniform cloth swatches in an aqueous detergent solution containing the antibacterial agents or combinations to be tested, rinsing, drying the swatches in a microorganism-free atmosphere, and after drying, inoculating the swatch with a suspension of test organisms in serum (0.1 ml. containing approximately 5000 organisms). After the inoculation with the serum suspension, the swatches are again allowed to dry and then they are planted in an agar medium Petri plate with the inoculated surface up and an overlay of agar nutrient is added over the fabric. The Petri plates are then incubated at 37 C. for 48 hours and thereafter bacterial colony counts on the cloth swatches are made using a lowpower dissection microscope. The relative ability of the treated fabric to inhibit growth or kill the organism is a measure of the antibacterial activity of the particular agent or combination being tested.

EXAMPLE I Example I demonstrates the criticality of the length of the alkyl group in the alkyl phenol component of the compositions of this invention. To separate portions of a detergent composition consisting of 17.5% tetrapropylene alkyl benzene sulfonate, 47.5% sodium tripolyphosphate, and sodium sulfate and minor additives were added, by weight of the detergent composition, 0.05% 3-trifluoromethyl-4,4-dichlorocarbanilide (TFC), or 0.05% bis(2-hydroxy-3,5,6-trichlorophenyl) methane (6-11), or 1.75% of alkyl phenol compounds of varying alkyl group lengths as indicated below in Table I, and cloth swatches were washed in aqueous solutions of these respective compositions. Like swatches were washed in aqueous solutions of the detergent composition having the formula above to which had been added, by Weight of the detergent composition, 1.75% of the alkyl phenol indicated in Table I below and in combination therewith either .05% TFC, or 0.05% 6-11. All of the washed swatches were rinsed and inoculated with S. aureus or ganisms and treated according to the method of Quinn. In Table I the lower number of surviving colonies indi- It can be observed from the above table that para alkyl phenol compounds by themselves have essentially no antibacterial activity as measured by the Cloth Protection Test. It can be seen, however, that when used in combination with TFC or G-ll, two antibacterial compounds representative of those which can be used as the primary antibacterial agent in the compositions of this invention, those p-alkyl phenol compounds having an alkyl group ranging from 9 to about 12 carbon atoms act to enhance the antibacterial activity of TIC and G-ll to a significant degree. Similar results can be achieved using the para alkyl phenols having an alkyl group ranging from 9 to about 12 carbon atoms in combination with other primary antibacterial agents described herein.

EXAMPLE II This example demonstrates the enhanced antibacterial activity obtained by the combination of p-tetrapropylene phenol and p-dodecyl sulfonyl phenol, two representative alkyl phenols of this invention with, respectively, 3,4,4- trichlorocarbanilide. bis(2-hydroxy 3,5,6-trichlorophenyl) methane, and 3-trifluoromehyl-4,4-dichlorocarbanilide, three representative primary antibacterial agents used in the compositions of this invention. The antibacterial compostions were employed in detergent compositions as indicated and the test procedure was the same as is described in Example I.

In addition to the indicated percentage of C ABS in each detergent composition, the detergent composition consisted of 50% sodium tripolyphosphate, and the balance sodium sulfate and minor additives, to which was added the indicated percentage of alkyl phenol and/or primary antibacterial agent, the percentage of alkyl phenol and primary antibacterial agent being based on the weight of the detergent composition before the addition of the alkyl phenol enhancers or primary antibacterial agents.

In Table II below TCC refers to 3,4,4'-trichlorocarbanilide; TFC refers to 3-trifluoromethyl-4,4-dichlorocarbanilide; G-11 refers to bis(2-hydroxy-3,5,6-trichlorophenyl) methane; and C ABS refers to tetrapropylene benzene sulfonate.

TABLE II.-ENHANCED CLOTH PROTECTION OF TOO, G-ll AND TFC IN COMBINATION WITH p-TETRAPROPYLENE PHENOL AND p-DODECYL SULFONYL PHENOL S. aureus Colonies Percent 1 Percent 1 surviving Percent p-tetraprop-dodecyl Percent 1 per sq. C12 ABS pylone sulfonyl Antibacterial inch of Product Surfactant phenol phenol Agent Cloth 17. 5 None None None 3, 080 17.5 None None 0.1 TCC 180 17.5 None None 0.05 TCC- 2, 720 17.5 None None 0.01 TCC. 2, 370 15.9 1.6 None 0.1 TCC. 2 15. 9 1. 6 None 0.05 TCC. 17 15. 9 1. 6 None 0.01 TCC 220 15. 9 1.6 None 0.001 TCC. 860 15.9 1. 6 None None 1, 850 14.6 2.9 None 0.1 TCC.. l 14. 6 2. 9 None 0.05 TC C 10 14. 6 2. 9 None 0.01 63 14. 6 2. 9 None 0.00 75 14. 6 2.9 None None 120 14. 6 None 2. 9 0.1 TCC- 8 14. 6 None 2. 9 0.05 TC 0 54 14.6 None 2. 9 0.01 TCC- 2, 030 14.6 None 2. 9 None... 2, 640 17.5 None None 0.1 G11. 220 17. 5 None None 0.05 1, 410 17.5 None None 0.01 2, 800 15. 9 1. 6 None 0.1 G-11 15. 9 1. 6 None 0.05 15.9 1. 6 None 0.01 1,280 15. 9 1. 6 None 0.001 1, 020 15.9 1. 6 None None 1, 850 14. 6 2.9 None 0.1 1 14. 6 2. 9 None 0.05 3 14. 6 2. 9 None 0.01 30 14. 6 2. 9 None 0.001 120 14.6 2. 9 None Non 60 14.6 None 2. 9 0.1 G 0 14. 6 None 2. 9 0.05 2 14. 6 None 2. 9 0.01 1, 820 14. 6 None 2. 9 0.00 2, 100 14. 6 None 2. 9 None..- 2, 640 17.5 None None 0.1 T 11 17. 5 None None 0.05 2, 410 15.9 1. 6 None 0.1 T 0 15.9 1. 6 None 0.05 1 15. 9 1. 6 None 0.01 340 15.9 1. 6 None 0.001 800 15. 9 1. 6 None None 690 14. 6 2.9 None 0.1 T C 0 14. 6 2. 9 None 0.05 0 14. 6 2. 9 None 0.01 0 14. 6 2. 9 None 0.001 0 14. 6 2. 9 None None 4 14.6 None 2. 9 0.1 TFC. 1 14. 6 None 2. 9 0.05 TFO 17 14. 6 None 2. 9 0.01 TFO 366 14. 6 None 2. 9 0.001 TFC 2, 285 14.6 None 2 9 None 1, 624

1 Percentage based on weight of the detergent composition.

From the above table it can be seen that the alkyl phenol compounds significantly enhance the antibacterial activity of the primary antibacterial agents. For example, 180 colonies of S. aureus per sq. in. survived on cloth swatches washed in an aqueous solution of Product 2a which contained no alkyl phenol and 0.1 TCC. 1850 colonies of S. aureus per sq. in survived on cloth swatches washed in an aqueous solution of Product 32. which contained p-tetrapropylene phenol at the 1.6% level but no TCC. But only 2 colonies of S. aureus per sq. in. survived on cloth swatches washed in an aqueous solution of Product 3a which contained 1.6% p-tetrapropylene phenol and 0.1% TCC; demonstrating that p-tetrapropylene phenol, 2,6-dichloro-p-nonyl phenol, pdecyl phenol or the two compounds are used in combination.

Highly improved antibacterial properties can be achieved using other alkyl phenols such as p-nonyl phenol, 2,6-dichloro-p-nonyl phenol, p-decyl phenol, or p-decyl sulfonyl phenol, in combination with other pri mary antibacterial agents such as 5,4-dichlorosalicylanilide, 5 bromosalicyl 3,4 di(trifluoromethyl) anilide, 3'-bromo-3,4-dichlorocarbanilide, bis(2-hydroxy-3,5,6-trichlorophenyl) sulfide; bis(dibenziodolium) sulfate, diben- Ziodolium lactate, 3,7-dimethyldibenz(b,e) (1,4) oxiodinium chloride, and phenyl mercuric acetate. Also such primary antibacterial agents as tri-n-propyltin acetate, tributylin oxide, neomycin, neomycin sulfate, neomycin palmitate, and triphenylbisumth can be used to obtain greatly improved antibacterial activity.

EXAMPLE III This example demonstrates the enhanced antibacterial activity obtained when p-tertaphopylene phenol is used in combination with the primary antibacterial agents shown below. The test method used was the same as is described in Examples I and II. Duplicate tests were run using cloth swatches inoculated with E. coli and S. aureus.

In Table III below C ABS refers to tetrapropylene benzene sulfonate; TCC refers to 3,4,4'-trichlorocarbanilide; TFC refers to 3-trifluoromethyl-4,4dichlorocarbanilide; DTC-l refers to 3,4-dichloro-3-trifluoromethylcarbanilide; DTC-Z refers to 3,5-dichloro-3-trifluoromethylcarbanilide; BSA refers to a mixture of 5,4-di, and 3,5,4- tribromosalicylanilide; and G-S-S refers to bis(2-hydroxy- 3,5-dichlorophenyl) sulfide.

In addition to the indicated amount of C ABS (17.5%), the detergent composition used in this example consisted of 50% sodium tripolyphosphate, and 32.5% substantially sodium sulfate and minor additives. To individual proportions of the composition were added the alkyl phenol and/or primary antibacterial agent in the percentage quantities indicated below, the percentages being based on the weight of the detergent composition.

C ABS Surfactant at 17.5% of Detergent Composition with Percent Alkyl Phenol and Primary Antibacterial Agent Indicated Bacterial Colonies Percent Surviving Per Sq. p-Tetra- In. Cloth propylene Percent Primary Anti- Phenol bacterial Agent S. aureus E. 0012 1 1. 75 None 1, 205 3, 040 2 0.5 do. 2,530 3, 470 3"- 1.75 005 T 17 2,195 4.-. 0 .....(1 2,720 2,230 5 1.75 01 G*ll 2,130 0 do 215 2, 450 7 1.75 005TFC 1 1,020 8"-.. 0 do 1, 060 1,725 9 0.5 0.1 DTO1 8 2, 320 10 0 do 44 2,200 11 0. 5 0.1 D'IC2. i 0 1, 960 12--.- 0 .d0 9 3,140 13- 1. 75 1.0 lgis (dihenziodolium)sul- 730 43 a e. 14- 0. 5 260 0 15 0 635 50 16.- 1.75 31 2, 860 17.-.- 1.75 210 2, 630 18 O 2, G10 2, 630 19.- 0 2, 810 2, 860 20.-.- 1. 75 14 2, 410 21.. 0 (l0 430 2, 410 22 1. 75 0.1525 each of BSA and G-E- 104 2, 030 23.- 0 d0 2,880 2,000 24 1. 75 0.05 each of BSA and '1FO 5 2, 330 25.-.. 0 d0 500 2, 770 26.-.. 1. 75 0.125 each of BSA and AgNOa 03 050 27 0 .-do 2, 260 1,090 28...- 1. 75 0.05 each of BSA and neo- 11 2, 180

mycin sulfate.

*The percent alkyl phenol and primary antibacterial agent present is based on the weight of the detergent composition.

By examining the above table it can be seen that the alkyl phenol compounds of this invention, represented above by p-tetrapropylene phenol, enhance the antibacterial activity of representative primary antibacterial agents. For example, 1205 colonies of S. aureus per sq. in. survived on cloth swatches washed in an aqueous solution of Composition 1 containing 1.75% p-tetrapropylene phenol and no primary antibacterial agent, and 2720 colonies of S. aureus per sq. in. survived on swatches washed in an aqueous solution of Composition 4 which contained no alkyl phenol and TCC at the 0.05 level; however, only 17 colonies of S. aureaus per sq. in. survived on cloth swatches washed in an aqueous solution of Composition 3 which contained 1.75% p-tetrapropylene phenol and 0.05% TCC. Thus enhanced activity is shown. 0

Similar comparisons can be made for the other combinations in this example. Similar results can be obtained by using alkyl phenols such as 2-chloro-p-nonyl phenol, pdodecyl sulfonyl phenol, tetrachloro-p-dodecyl phenol, pundecyl sulfonyl phenol, and S-chloro-p-nonyl phenol in place of p-tetrapropylene phenol in the compositions in the table.

As mentioned herein the antibacterial compositions of this invention can be incorporated into soap and anionic, nonionic, amphoteric and ampholytic synthetic detergent formulations.

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 animal fats and oils (e.g., palm oil, coconut oil, babassu oil, soybean oil, caster 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 oils or by the neutralization of the free fatty acids which are prepared in a separate manufacturing process.

The non-soap 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 in its molucular structure an alkyl radical 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 used in conjunction with the mixtures of this invention, are the sodium or potassium alkyl sulfates, especially those derived by sulfation of higher alcohols produced by reduction of tallow or coconut oil glycerides; sodium or potassium alkyl benzene sulfonates, especially those of the types described in US. Letters Patents 2,220,009, granted Nov. 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 By'erly, U.S. Letters Patent 2,486,921, granted Nov. 1, 1949, and Strain, U.S. Letters Patent 2,486,922, granted Nov. 1, 1949.

A minor amount, totaling about 2% of a 1:4 mixture of 3,4,4'-trichlorocarbanilide and p-dodecyl sulfonyl phenol, 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 products 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 oxide condensates of alkyl phenols, e.g., the condensation products of alkyl phenols having from 6 to 12 carbon atoms in the alkyl group, either straight or branched chain, 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 derived 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 diamine. 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 pr duct of thyl 13 ene diamine and excess propylene oxide, said base having a molecular weight of the order of 2500 to 3000, are satisfactory.

Further satisfactory nonionics include the condensation product of aliphatic alcohols having from 8 to 18 carbon atoms, either straight chain or branched chain, with ethylene oxide, 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 T is an aliphatic hydrophobic group containing from about 8 to about 18 carbons, X is an anion selected from the group consisting of sulfonate, su fate and carboxy radicals, Z is an intermediate group joined to an R by a basic nitrogen atoms, and M is a cation to neutralize the charge of the anion. 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 of coconut alcohol or fatty acid.

Additional ampholytic detergents suitable for use in this invention are disclosed in Surface Active Agents and Detergents by A. M. Schwartz, J. S. Perry and I. Berch, Interscience Publishers, New York, 1958, vol. II on pages 138-144.

Other detergent compounds which can be used in the practice of this invention include the arnphoteric sulfated and sulfonated quaternary ammonium compounds known as sultaines or sulfo-betaines. These compounds 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-N-hexadecylammonio) 2 hydroxypropane-l-sulfonate, 3 (N,N-dimethyl-N-alkylammonio)-2- hydroxypropane-l-sulfonate, the alkyl group being derived from tallow alcohol, 3-(N,N-dimethyl-N-dodecylam monio)-propane-l-sulfonate, and 3-(N,N-dimethyl-N- hexadecylammonio)-propane-1-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 distribution of agents throughout the whole mass.

Regular use of a conventional soap bar (mixtures of potassium and sodium salts of tallow and coconut fatty acids) containing 1.5% of an antibacterial mixture of this invention, e.g., 0.5% 3,4,4-trichlorocarbanilide plus 1% p-tetrapropylene phenol, results in substantial reductions in the bacterial population of the skin and thereby markedly reduces body odor attributable to the bacterial degradation of perspiration.

EXAMPLE IV A sample formula for a milled toilet detergent bar which can be prepared by means known and used in the art is as follows: (the term middle-cut as used herein refers to that fraction of distilled coconut alcohol which consists predominantly of lauryl and myristyl alcohols).

Percent by weight Potassium alkyl sulfate (alkyl group derived from the middle cut of alcohols obtained by the Percent by weight Inorganic salts 5.5 3,5,4'-tribromosalicylanilide .75 p-Nonyl phenol 1.0 Moisture 8.0

Miscellaneous Balance This bar inhibits the development of odor and reduces the .number of bacteria on the skin. The p-nonyl phenol in the above formula can be replaced by p-dodecyl sulfonyl phenol, p-dodecyl phenol, or tetrachloro-p-dodecyl phenol, for example, and substantially the same results are achieved.

EXAMPLE V A granular built synthetic detergent composition having the following formulation can be prepared by spray drymg.

Percent by Weight SOCllLll'Il alkyl benzene sulfonate (the alkyl radical averaging about 12 carbon atoms and being The is composition imparts considerable antibacterial activity to fabrics washed in an aqueous solution of it. Substantially the same results can be achieved by replacing bis(2-hydroxy-3,5,6-trichlorophenyl) methane in the above formula With 3,4,4'-tribromocarbanilide, 3-trifiuoromethyl-4,4'-dichlorocarbanilide, 5 chlorosalicyl-3- trifiuoromethyl-4-chloroanilide, triphenylbismuth, bis(dibenziodolium) sulfate, bis[3,7-dichlorodibenz(b,e) (1,4) oxiodiniumlsulfate, phenyl mercuric acetate, tri-n-propyltin acetate, or N-poly-(l-naphthylmethylene) neomycin.

In the formula above the detergent active can be replaced by the sodium salt of the sulfated condensation product of one mole of coconut alcohol with about three moles of ethylene oxide, sodium dodecyl sulfate, the condensation product of 1 mole dodecyl phenol with about 15 moles ethylene oxide, the condensation product of 1 mole of coconut alcohol with about 15 moles of ethylene oxide, disodium lauryl beta-iminodipropionate, disodium lauryl beta-aminodipropionate, 3-(N,N-dimethyl-N-dodecylammonio) propane 1 sulfonate, and 3-(N,N-dimethyl N hexadecylammonio)-propane-l-sulfonate, or mixtures thereof, without materially affecting the pr0perties of the composition.

In the preceding working examples p-tetrapropylene phenol is employed with the two carbanilides, TFC or TCC, in the following ranges: 1.6 to 2.9 parts of p-tetrapropylene phenol with 0.1 to 0.001 parts of TFC; 1 to 2.9 parts of p-tetrapropylene phenol with 0.5 to 0.001 parts of TCC.

The invention has been described above in conjunction with various illustrative examples of antibacterial compositions, toilet and laundry detergents. It will be obvious to those skilled in the art, however, that the mixtures exhibiting enhanced activity can also be beneficially employed in such products as shampoos, antiseptic ointments, foot powders, and the like.

What is claimed is:

1. An antibacterial composition comprising an antibacterial-enhancer combination selected from the group consisting of (a) 1.6 to 2.9 parts of p-tetrapropylene phenol and 0.1 to 0.001 parts of 3-trifluoromethyl-4,4-dichlorocarbanilide and (b) 1 to 2.9 parts of p-tetrapropylene phenol and 0.5 to 0.001 parts of 3,4,4-trichlorocarbanilide.

(References on following page) References Cited UNITED STATES PATENTS OTHER REFERENCES gsgvgrfiijiiiiiii gggigg ALBERT T. MEYERS, Primary Examiner Leatherland. 5 V. C. CLARK, Assistant Examiner Molnar.

Cannon. US. Cl. X.R.

Zedler.

Gump 424347 10 252 106, 107, 424 346 McNulty et a1. 260 -624 X Reller et a1. 424-322 X Markgraf et a1. 424-337 X Merck Index, Merck, 1960, pp. 711, 712, 804.

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US5256334 *Feb 28, 1992Oct 26, 1993The Research Foundation Of The State University Of New YorkTriphenylbismuth disoersed in polymer; medical and dental equipment; nonleachable
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Classifications
U.S. Classification514/596, 510/319, 510/389, 510/388, 510/387, 510/141, 510/131, 514/728
International ClassificationA01N41/10, A01N31/08
Cooperative ClassificationA01N31/08, A01N41/10
European ClassificationA01N41/10, A01N31/08