US3152039A

US3152039A - Germicidal compositions

Info

Publication number: US3152039A
Application number: US71171A
Authority: US
Inventors: Guy C Mattson
Original assignee: Dow Chemical Co
Current assignee: Dow Chemical Co
Priority date: 1960-11-23
Filing date: 1960-11-23
Publication date: 1964-10-06
Anticipated expiration: 1981-10-06

Description

United States Patent Offiee 3,152,039. Patented Oct. 6, 1964 3,152,039 GERMICIDAL COMPOSITIONS Guy C. Mattson, Midland, Mich, assignor to The Dow Chemical Company, Midland, Mich., a corporation of Delaware No Drawing. Filed Nov. 23, 1960, Ser. No. 71,171 13 Claims. (Cl. 167-31) The invention relates to germicidal compositions and more particularly is concerned with germicidal compositions comprising brominated salicylanilides dissolved in an alcoholic solvent to which has been added an alkanolamine.

Brominated salicylanilides such as 3,5,4'-tribrornosalicylanilide, 3,5-dibromosalicylanilide, 4',5-dibromosalicylanilide and mixtures of such triand dibrominated compounds exhibit excellent germicidal properties. However, the utility of these substances is limited to some extent by their low solubility in most common solvents, e.g. ethyl alcohol, propylene glycol, glycerine, isopropanol, acetone, and the like.

This low solubility not only limits the use of these substances in compositions wherein it is desirable to have the germicide in a dissolved state, i.e., shampoos, deodorants, etc., but also makes diificult the incorporation of these germicides into compositions where they are used in the insoluble state such as in soap and detergent bars, powders and flakes.

Now unexpectedly it has been found that the solubility of 3,5,4-tribromosalicylanilide, di-dibromosalicylanilides and mixtures of the triand di-brominated materials in common alcoholic type solvents can be greatly increased by adding a small amount of an alkanolamine thereto.

The compositions of the instant invention comprise 3,5,4-tribromosalicylanilide and a dibromosalicylanilide in a solvent mixture of a monohydroxy aliphatic hydrocarbon alcohol, polyhydroxy aliphatic hydrocarbon alcohol or a polyglycol and a mono-, di or trialkanolamine wherein the amount of the alkanolamine in the composition ranges up to about 40 weight percent of the solvent mixture.

Preferably, in the instant composition the triand dibromosalicylanilides will be used as a mixture containing from about 25 to about 98 weight percent of the tribrominated compound and from about 75 to about 2 weight percent of the dibromosalicylanilide and desirably will be used as a mixture containing about 80 parts by weight of the tribromosalicylanilide and about 20 parts by Weight of the dibromosalicylanilide. The actual concentration of the members used in the instant germicidal composition ordinarily will be limited to those amounts below which saturated solutions are formed with the solvents. The monoand polyhydroxy alcohols, polyglycols and alkanolamines preferably all will have alkyl groups selected from those members containing 2 and 3 carbon atoms and the amount of alkanolamine to be used desirably will range from about 5 to about 20 weight per cent of the weight of the solvent mixture.

Of the common solvents and carriers for brominated salicylanilides, hydrocarbon aliphatic alcohols such as absolute ethanol, ethylene glycol, 95 percent ethanol, polyethylene glycols, propanol, isopropanol, glycerine, polypropylene glycols, propylene glycol and the like are particularly adapted for incorporation into conventional soap and detergent compositions. By the term soap is meant sodium salts of various fatty acids of natural oils and fats and mixtures of such sodium salts. This term is also meant to include compounds of these fatty acids wherein other metal or basic radicals are present instead of sodium. By the term detergent is meant a material which has a cleansing action like soap but is not derived directly from fatty acids. (See Rose and Rose, The Condensed Chemical Dictionary, 5th edition, Reinhold Publishing Corporation, New York.) However, the brominated salicylanilides enjoy only a limited solubility in most of these solvent materials. For example, the solubility of a mixture of 3,5,4'-tribromosalicylanilide (about weight percent) and 3,S-dibromosalicylanilide (about 20 weight percent) based on grams of the salicylanilide mixture per 100 grams of solvent at 25 C. is; 0.35 gram in propylene glycol, 0.012 gram in glycerine, 0.92 gram in isopropanol, 0.03 gram in percent ethanol, and 0.03 gram in absolute ethanol. The solubility in the polyglycols is somewhat improved, e.g. 5.38 grams per grams of a polypropylene glycol having an average molecular weight of about 4000 and 20.9 grams per 100 grams of a polyethylene glycol of average molecular weight about 400. However, with all of these solvents, replacement of only a small amount of the alcoholic member by an alkanolamine has been found to unexpectedly increase the solubility of the brominated salicylanilide therein. To illustrate, 100 grams of a solution of 95 percent ethanol (90 weight percent) and diethanolamine (10 weight per cent) was found to dissolve 37 grams of the 80 weight per cent 3,5,4,-tribromo- 20 weight percent 3,S-dibromosalicylanilide mixture.

Compositions containing larger amounts of the alkanolamines show still increased solubility of the brominated salicylanilides. However, for most applications, and, particularly when the germicide compositions are used in toilet and laundry soaps, it is desirable to keep the alkanolamine content relatively low, e.g. below about 20 percent of the total composition.

The compositions will be used in soaps at an eifective germicidal concentration, e.g. in amounts ranging from about 0.05 to about 1.0 weight percent, based on the total brominated salicylanilide concentration present in the salicylanilidealcohol or polyglycolalkanolamine solution.

The actual preparation of the instant germicidal compositions can be carried out by various conventional techniques. For example, the alkanolamine can first be added to the alcoholic solvent member and the brominated salicylanilide can then be added to the mixed solvent and dissolved therein. Alternatively, a given amount of a brominated salicylanilide or salicylanilide mixture can be added to an alcohol and suflicient alkanolamine then be added to this mixture to produce the desired solution.

The instant compositions have been found in a standard microorganism growth control test to give growth inhibition to a number of common microorganisms at about the same level as the brominated compounds themselves. Such action demonstrates that the germicidal activity of the brominated salicylanilides is not lost by their incorporation into these compositions.

Toxicological studies have indicated that there appears to be no contraindications for the use of these solutions in formulations designed for direct human contact, e.g.

3 shampoos, deodorants, toilet soaps and detergents and the like.

The following examples will serve to further illustrate the compositions of the instant invention but are not meant to limit it thereto.

Example 1 A weighted sample of a mixture containing about 80 parts 3,5,4'-tribromosalicylanilide and about 20 parts 3,5- dibromosalicylanilide was placed in a beaker. Ninetyfive percent ethanol-alkanolamine solvent was added with stirring at room temperature (about 25 C.) until complete dissolution of the sample occurred, as determined by visual observation.

The results of test runs using 90/10 (by volume) mixtures of 95 percent ethanol-diethanolamine and 95 percent ethanol-triethanolamine are presented as follows:

A weighted sample of the brominated salicylanilide mixture described in Example 1 was added at about room temperature, 25 C., to a given amount of an alcoholic solvent contained in a flask. The amount of the salicylanilide mixture used in all cases was markedly in excess of that which was soluble in the given amount of the alcohol. Controlled amounts of an alkanolamine were added with stirring to the mixture. This addition was stopped at the point where complete solubility of the salicylanilides in the resulting alcohol-alkanolamine solvent mixture was observed. The following table lists the resulting compositions obtained from several test runs.

lowing table lists the resulting germicidal solution compositions:

Brominated Sali- Alcohol Alkanolamine ylanilides Composition N 0. Parts By Weight 1 3,5,4'-Tribromo- Propylene GlycoL Monoethanolasalicylanilide] mine. 3,5-dibromosalicylanilide Glycerine Do. Ethanol (95%). Do. Propylene Glycol- Monolsopropanolamine. Glyceriue Do. Ethanol (95%)--.- Do.

Propylene Glycol- Dusopropanolamine. Glycerine Do.

A second series of tests was run utilizing the same components as above, but in this series the solvent pair contained 30 parts by weight of the amine and 50 parts by weight of the alcoholic material. This is equivalent to a solvent containing about 37.5 weight percent of amine component. To these solvent pairs was added parts by weight of the brominated salicylanilide mixture.

The resulting compositions all were found to form solutions except for the system employing the monoisopro panolamine and glycerine solvent pair.

Example 4 The germicidal activity of several compositions of the instant invention was studied utilizing a standard bacteriostatic test. In this test, a predetermined quantity of the germicidal composition containing an 80-20 mixture of 3,5,5'-tribromo and 3,5-dibromosalicylanilide, and based on actual brominated salicylanilide concentration, was incorporated into a melted Difco nutrient agar medium. The agar was then hardened. One of a variety of microorganisms was streaked onto the hardened medium and the culture then was incubated at 30 C. for 72 hours.

Alcoholic Component Alkanolamine Component Solubility Bromin- Salicyl- Rlm No. ated Salianilide/ cylanilide, solvent,

grams Type Grams Type Grams g.ll00 g 1 Polyethylene Glycol Triethanolamine 5 54. 5 2 50 50 10 82. 3 3 10 Glycerine 186 4. 5 5. 25

1 Average molecular weight=400.

Example 3 A number of stock solvent solutions were prepared containing 15 parts by weight of a given alkanolamine and 75 parts by weight of a given alcoholic member. To each of these solutions, suflicient quantities of the brominated salicylanilide mixture described in Example 1 were added to give a resulting composition containing about 10 percent by weight of the brominated salicylanilide. In all cases, complete solubility of the salicylanilide mixture was found in the solvent pair. The folefliciency.

Germieidal Composition I (p.p.m. llI (p.p.m. Control 3 Run No. Microorganism (p.p.m.)

Inh No Inh 4 No 11111 4 No Inh 5 11111 5 Inh 5 Micrococcus pyogenes 5 5 5 (staph. aureus).

Salmonella typhosa 50 01% 50 50 Aerobacter aerogenes .01% 50 .01% .01% Erwim'a carolovora 50 10 50 10 50 (4 80-20 3,5,4'-tribromo-, 3,5-dibromosalicylanilide (40 parts by Wt.), Propylene Glycol 5 parts by at), Diethanolamine parts by wt parts by 1.), Monoethanolamine (40 parts by wt.).

3 80 parts 3,5,4-tribromosalicylanilide, parts 3,fi dibromosalicylanilide.

4 Lowest concentration of germicide to give growth inhibition. 5 Highest concentration of germicide that gave no growth inhibition. 6 Unless shown otherwise.

In a manner similar to that described for the foregoing examples, a mixture of about 98 parts by Weight of 3,5,4'-tribrominated salicylanilide and about 2 parts by weight of 4',5-dibromosalicylanilide and a mixture containing about weight percent of 3,5,4-tribromosalicylanilide and about 75 weight percent of 3,5-dibromo salicylanilide can be dissolved in alcoholic-alkanolamine solvents as defined herein to yield effective germicidal compositions.

Various modifications can be made in the compositions of the present invention without departing from the spirit or scope thereof for it is understood that I limit myself only as defined in the appended claims.

I claim:

1. A germicidal composition comprising a solution of a mixture of 3,5,4-tribromosalicylanilide and a dibromosalicylanilide in a mixed alcoholic-alkanolamine solvent, said mixed solvent dissolving markedly increased amounts of the brominated salicylanilide mixture over that dissolvable by the alcoholic component alone, the alcoholic component of said solvent being a member selected from the group consisting of monohydroxy aliphatic hydrocarbon alcohols, polyhydroxy aliphatic hydrocarbon alcohols and polyglycols having an alkyl group containing from 2 to 3 carbon atoms, the alkanolamine being a member selected from the group consisting of mino-, diand trialkanolamines wherein the alkyl group contains from 2 to 3 carbon atoms and the amount of said alkanolamine in the solvent mixture being up to percent of the weight of said solvent mixture.

2. A germicidal composition comprising a solution of a mixture of 3,5,4'-tribromosalicylanilide and a dibromosalicylanilide in a solvent mixture of an alcohol and an alkanolamine, said mixture of brominated salicylanilides containing from about 25 to about 98 percent of the tribrominated compound and from about 75 to about 2 weight percent of the dibromosalicylanilide and said mixture being present in a concentration below which said solution is saturated with said mixture, said solvent mixture dissolving an amount of the brominated salicylanilides greater than that dissolved by the alcoholic component alone and said solvent mixture comprising a mixture of (1) a member selected from the group consisting of monohydroxy aliphatic hydrocarbon alcohols, polyhydroxy aliphatic hydrocarbon alcohols and polyglycols having an alkyl group containing from 2 to 3 carbon atoms and (2) a member selected from the group consisting of mono-, di and trialkanolamine having an alkyl group containing from 2 to 3 carbon atoms, the alkanolamine comprising up to about 40 weight percent of the weight of the solvent mixture.

3. A germicidal composition comprising a solution of a mixture containing about 80 parts by weight of 3,5,4- tribromosalicylanilide and about 20 parts by weight of a dibromosalicylanilide dissolved in a mixed alcoholicalkanolamine solvent, the brominated salicylanilide mixture being present in said solution at a concentration below which said solution is saturated with said mixture, said mixed alcoholic-alkanolamine solvent comprising (1) a member selected from the group consisting of monohydroxy aliphatic hydrocarbon alcohols, polyhydroxy aliphatic hydrocarbon alcohols and polyglycols and (2) a member selected from the group consisting of monodiand trialkylamines wherein the alcoholic member and amine each have alkyl groups containing from 2 to 3 carbon atoms, said alkanolamine comprising from about 5 to about 20 percent of the weight of said solvent mixture, and said solvent mixture dissolving markedly increased amounts of said brominated salicylanilide mixture over that dissolved by the alcoholic component alone.

4. A soap composition which comprises soap having an efiective germicidal concentration of a mixture of 3,5,4-tribromosalicylanilide and a dibromosalicylanilide in a solvent, said mixture of salicylanilides containing from about 25 to about 98 percent of the tribrominated compound and from about to about 2 weight percent of the dibromosalicylanilide and said mixture being present in a concentration below which said solution i saturated with said mixture, said solvent comprising a mixture of (1) a member selected from the group consisting of monohydroxy aliphatic hydrocarbon alcohols, polyhydroxy aliphatic hydrocarbon alcohols and polyglycols having an alkyl group containing from 2 to 3 carbon atoms and (2) a member selected from the group consisting of mono-, diand trialkanolamines having an alkyl group containing from 2 to 3 carbon atoms, the alkanolamine comprising up to about 20 weight percent of the weight of the solvent mixture.

5. A germicidal solution which comprises:

(a) up to about 10 parts by weight of a mixture containing about percent, 3,5,4'-tribromosalicylanilide and about 20 percent 3,S-dibromosalicylanilide,

(b) about 75 parts by weight of an alcoholic member selected from the group consisting of monohydroxy aliphatic hydrocarbon alcohols, polyhydroxy aliphatic hydrocarbon alcohols and polyglycols having an alkyl group containing from 2 to 3 carbon atoms, and

(0) about 15 parts by weight of an alkanolamine selected from the group consisting of mono-, diand trialkanolamines wherein the alkyl group contains from 2 to 3 carbon atoms.

6. A germicidal solution which comprises:

(a) up to about 20 parts by weight of a mixture containing about 80 percent 3,5,4-tribromosalicylanilide and about 20 percent 3,S-dibromosalicylanilide,

(b) about 30 parts by weight of an alkanolamine selected from the group consisting of mono-, diand trialkanolamines wherein the alkyl group contains from 2 to 3 carbon atoms, and

(0) about 50 parts by weight of an alcoholic member selected from the group consisting of monohydroxy aliphatic hydrocarbon alcohols, polyhydroxy aliphatic hydrocarbon alcohols and polyglycols having an alkyl group containing from 2 to 3 carbon atoms.

7. A germicidal solution consisting essentially of:

(a) a mixture of about 80 parts by weight 3,5,4'-tribromosalicylanilide and about parts by weight 3,5-dibromosalicylanilide, and

(b) a solvent of 95 ethanol-diethanolamine, said solvent comprising on a volume basis about 90 parts of said 95% ethanol and about 10 parts diethanolamine, said solvent of said ethanol-diethanolamine dissolving at about C. up to about 37 grams of said brominated salicylanilide mixture per 100 milliliters of said ethanol-diethanolamine solvent.

8. A germicidal solution comprising:

(a) up to about parts by Weight of a mixture containing about 80 percent 3,5,4'-tribromosalicylanilide and about 20 percent 3,5-dibromosalicylanilide,

(b) about 50 parts by Weight polyethylene glycol, and

(c) from about 5 to about 10 parts by weight triethanolamine.

9. A germicidal solution comprising:

(a) up to about 10 parts by weight of a mixture containing about 80 percent 3,5,4'-tribromosalicylanilide and about 20 percent 3,S-dibromosalicylanilide,

(b) about 186 parts by weight glycerine, and

(c) about 4.5 parts by weight triethanolamine.

10. A germicidal solution which comprises:

(a) up to about 40 parts by weight of a mixture containing about 80 percent 3,5,4'-tribrornosalicylanilide and about 20 percent 3,5-dibromosalicylanilide,

(b) about parts by weight propylene glycol, and

(0) about 15 parts by weight diethanolamine.

11. A germicidal solution which comprises:

(a) up to about 40 parts by weight of a mixture containing about 80 percent 3,5,4'-tribromosalicylanilide and about 20 percent 3,S-dibromosalicylanilide,

(b) about 20 parts by weight 95% ethanol, and

(c) about 40 parts by weight monoethanolamine.

12. A detergent composition which comprises detergent having an effective germicidal composition of a mixture 8 of 3,5,4'-tribromosalicylanilide and a dibrornosalicylanilide in a solvent, said mixture of salicylanilides containing from about 25 to about 98 percent of the tribrominated compound and from about to about 2 weight percent of the dibromosalicylanilide and said mixture being present in a concentration below which said solution is satu rated with said mixture, said solvent comprising a mixture of (1) a member selected from the'group consisting of monohydroxy aliphatic hydrocarbon alcohols, polyhydroxy aliphatic hydrocarbon alcohols and polyglycols having an alkyl group containing from 2 to 3 carbon atoms and (2) a member selected from the group consisting of mono-, diand trialkanolamines having an alkyl group containing from 2 to 3 carbon atoms, the alkanolamine comprising up to about 20 weight percent of the Weight of the solvent mixture.

13. A germicidal solution consisting essentially of:

- (a) a mixture of about parts by Weight 3,5,4'-tribromosalicylanilide and about 20 parts by weight 3,5-dibromosa1icylanilide, and

(b) a solvent of 95% ethanol-triethanolamine, said solvent comprising on a volume basis about parts of said ethanol and about 10 parts of triethanolamine, said ethanol-triethanolamine solvent dissolving at about 25 C. up to about 20 grams of said brominated salicylanilide mixture per milliliters of said ethanol-triethanolamine solvent.

References Cited in the file of this patent UNITED STATES PATENTS 2,485,339 Eijk Oct. 18, 1949 2,643,965 OBrien June 30, 1953 2,731,386 Reiner Jan. 17, 1956 2,865,861 Stephens Dec. 23, 1958 2,906,711 Stecker Sept. 29, 1959 2,948,684 Thiele Aug. 9, 1960 OTHER REFERENCES Sagarin: Cosmetics Science and Technology, published by Interscience Publishers, Inc., New York (1957),

pages 292, 293 and 296.

Claims

1. A GERMICIDAL COMPOSITION COMPRISING A SOLUTION OF A MIXTURE OF 3,5,4''-TRIBROMOSALICYLANILIDE AND A DIBROMOSALICYLANILIDE IN A MIXED ALCOHOLIC-ALKANOLAMINE SOLVENT, SAID MIXED SOLVENT DISSOLVING MARKEDLY INCREASED AMOUNTS OF THE BROMINATED SALICYLANILIDE MIXTURE OVER THAT DISSOLVABLE BY THE ALCOHOLIC COMPONENT ALONE, THE ALCOHOLIC COMPONENT OF SAID SOLVENT BEING A MEMBER SELECTED FROM THE GROUP CONSISTING OF MONOHYDROXY ALIPHATIC HYDROCARBON ALCOHOLS, POLYHYDROXY ALIPHATIC HYDROCARBON ALCOHOLS AND POLYGLYCOLS HAVING AN ALKYL GROUP CONTAINING FROM 2 TO 3 CARBON ATOMS, THE ALKANOLAMINE BEING A MEMBER SELECTED FROM THE GROUP CONSISTING OF MINO-, DI- AND TRIALKANOLAMINES WHEREIN THE ALKYL GROUP CONTAINS FROM 2 TO 3 CARBON ATOMS AND THE AMOUNT OF SAID ALKANOLAMINE IN THE SOLVENT MIXTURE BEING UP TO 40 PERCENT OF THE WEIGHT OF SAID SOLVENT MIXTURE.