US 2904468 A
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United States Patent Carl Henry Davis, Coral Gables, and Constantine G. Grand, Miami, Fla., assignors to Carlen Corporation, Miami, Fla., a corporation of Delaware No Drawing. Application April 13, 1954 Serial No. 422,970
6 Claims. (Cl. 16758) The present invention relates to germicides.
It is an object of the invention to provide a composition that exhibits high germicidal activity.
A specific object is to provide an improved trichomonicide.
Another object is to provide a concentrated composition that can be dispensed and subsequently diluted with water at the time of use.
A further object is to provide a process for disinfecting surfaces.
The above and other objects will become apparent in the course of the following description.
The general approach to the destruction of disease organisms is to seek a specific toxic agent which can be employed at an effective level without undesirable side effects. Most of the microbicides are highly toxic, irritating or allergenic to higher forms of life as well and are therefore limited as to usable concentrations and frequency of use.
There are also many cases in which pathogenic microbes are difficult to kill in their host because of the existence of natural conditions protective to the pathogenie organism at the, site of infection. An outstanding example of this is found in the vaginitis caused by Trichomonas vaginalis Donn. The irregular surface of the vaginal and cervical mucosa and the secretions normally present protect the organisms from attack by conventional germicides to such an extent that the infections stubbornly resist control. The usual treatment of this vaginitis is particularly diflicult since it requires frequent and prolonged disinfection by skilled professional personnel.
The germicidal composition of this invention has proven exceptionally effective in the treatment of trichomonad infections and is likewise useful against other microbic life. It has shown no evidence of undesirable side effects under conditions of use.
It has been discovered, in accordance with the invention, that the combination of a polyoxyethylene alkyl phenol non-ionic detergent, an active wetting agent, and a substituted amino acetic acid, chelating or sequestering agent for calcium produces a germicide. that exhibits exceptional utility in achieving the above named objects. The three components are readily soluble or dispersible in water and are compatible through wide ranges of proportions and at various dilutions.
The non-ionic detergent is a member of the class of polyoxyethylene alkyl phenols containing a lipophilic hydrocarbon group of at least 12 carbon atoms and at least 6 oxyethylene groups per lipophilic hydrocarbon radical, the lipophilic hydrocarbon and polyoxyethylene chain length being balanced to provide good detergency. Such compounds are well known in the detergent field. The preferred member of this class for, the purpose of this invention is a commercial polyoxyethylene nonyl phenol containing about 10 oxyethylene groups per mol. Other detergents that can be used are other polyoxyethylene alkyl phenols such as those derived from octyl, decyl or dodecyl phenol. V
The Wetting agent component used in the germicide is one of the salts of an organic sulfate or sulfonate that have strong Wetting properties. The members of this class are of several chemical types well recognized in the surface active agent art. The preferred wetting agent is sodium dioctyl sulfosuccinate. Others that can be used are the ammonium, alkali metal, lower alkylamine and alkylolamine salts of alkyl aryl sulfonic acids, for example, the isopropanolamine salt of dodecyl benzene sul fonic acid or the triethanolamine salt of alkyl aryl sulfonate sold by Atlantic Refining Company under the trade mark Ultra Wet 60L. Further suitable wetting agents are the corresponding salts of fatty alcohol sulfuric acid esters, for example, sodium lauryl sulfate or triethanolamine lauryl sulfate. Other wetting agents of the type of salts of dialkyl sulfosuccinic acid may also be used in place of the preferred sodium dioctyl sulfosuccinate.
The calcium chelating or sequestering agent comprising the third essential component of the germicide is one of the substituted amino acetic acids of commerce which are available as chelating agents in the form of their alkali metal salts. The preferred chelating agent is ethylene diamine tetra-acetic acid, particularly the tetra sodium salt of commerce.
The preferred composition at the present time has the following composition.
The composition is compounded by first preparing a 12% aqueous solution of the ethylene diamine tetraacetate. This solution is added to the polyoxyethylene nonyl phenol, which is liquid, after which the sodium dioctyl sulfosuccinate solution is added. Finally the water is added to make up the indicated volume. DIStlII-r ed water is employed throughout. After thorough mixing the product is a clear solution with a slight straw color.
This composition at a dilution in tap water of one part in 250, in vitro kills T. vaginalis under 30 seconds.
As the wetting agent in the compositions of the examples there can be used sodium lauryl sulfate or amine salts of alkyl aryl sulfonic acids in amounts correspond ing to the sodium dioctyl sulfosuccinate. Mixtures of these wetting agents can be employed if desired.
The advantage of the three component composition is illustrated by the following comparison. The tests were 48 hour culture with two drops of testsolution and checking under phase contrast microscope. The 'under alkyl phenol hydrocarbon radical wherein the alkyl group contains from 6 to 12 carbon atoms, said detergent containing at least 6 oxyethylene groups per lipophilic alkyl phenol hydrocarbon radical, the lipophilic hydrocarbon and polyoxyethylene chain length being balanced to provide good detergency, a wetting agent selected from the group consisting of salts of organic sulfates and organic sulfonates and a calcium chelating agent which is an Composition Tested v H Test Test No. I I Dilution Kill time sodium dioctyl sulfosucethylene diamine tetraacepolyoxyethylene nonyl 1 cinate, 25% aq'. solution tate Na, 12% aqosolution phenol I A Zparts/IOO parts water 0. 1/270 over 11:5 min- 11 es. R n 50 parts/100 parts water 1/270 Do. (7 n l/270 Do. 1),. 0- I 50 parts/100 parts water '80 seconds; 15.; 2 parts/100 parts water do 0 over minutes. F. n n I parts/100 parts water 1/270 Do. G "do 50 parts/100 parts water do 1/270 under 30 seconds.
NOTES Test A, at 3 minutes organisms swollen but none dead. No further change at end of 6 minutes. Some still alive at end of 15 minutes.
Test B, all flagellates became spherical under 3 minutes.
Test C,'some.flagellates alive after 15 minutes with very little evidence of change of form. 'I est D, most flagellates appeared dead within one minute but some alive to 80 seconds.
Occasional organism alive after 15 minutes.
Those that died became round first. After death they appeared as granular Test E, all flagellates became round within 3 minutes. Those that died were swollen but did not disintegrate. A few were alive at end of 15 minutes Test F most flagellated dead in 10 minutes but some alive after 15 minutes.
The relative proportions of the detergent, wetting and chelating agents can be varied within considerable limits. The detergent. should be the major component; On a solids basis it is preferably 70 to 90% of the composition. The chelating agent is preferably 5 to 15% of the composition. The wetting agent is needed only in small amount'and larger quantities appear to have no advantage. The wetting agent should preferably constitute from 0.5 to 5% of the solids of the composition]. It will be understood that for diiferent uses and different methods of dispensing and application variations in these proportions may be advisable.
The compositions of the invention are particularly useful as human trichomonicides. They are, however, useful also against other organisms that infect the human body. They may also be useful in veterinary medicine against trichomonads, such as T. foetus, and other organisms encountered in animals.
The usefulness of the compositions may be extended by employing them in conjunction with, for example, fungicides like thymol, and germicidal agents like acrifiavine. 'In conventional manner, the products can be colored and/ or perfumed if desired. I
u The invention also contemplates the process of disinfecting s urfaces by contacting them with aqueous solutions of the above described compositions. This process isemployed, for example, in the treatment of vaginitis by douching with a dilution of one part of the above presently preferred composition in 250 parts of Water. The process is also employed in preparing a skin area priortofmaking a surgical incision in which case the arcais scrubbedwith a higher concentration of the composition. The foregoing are all examples of topical application of the compositions of the invention.
Many variations of the compositions and processes described will be apparent to those skilled in this art.
What is claimed is: I
I 1.. An aqueous germicidal composition containing as ess'entialingredients a non-ionic detergent of the class of alkali metal salt of an amino acetic acid, said detergent, Wetting agent and chelating agent being present respectively in thIe following proportions by weight on a dry basis: 7090%;' 0.55% and 5 -15%. ff
2. The germicidal composition recited in claim 1 where;- in. said calcium chelating agent is a sodium salt' of' an amino acetic acid. I i 3. The germicidal composition recited in claim'l wherein said calcium chelating agent is ethylene' diam'ine tetraacetic acid sodium salt. Y I *5 I '4.".The processflof'dis infecting a skin surface which comprises contacting the surface with a dilute solution in 'water of an non-ionic detergent of the class of poly oxyeth'ylene alkyl phenols containing alipophilic "alkyl phenol hydrocarbon radical wherein the alkyl group con tains from 6 to 12 carbon atoms, said detergent'contain ing' at least 6' oxyethyl'ene groups per lipophilicfalkyl phenol hydrocarbon radical, the lipophilic hydrocarbon and polyoxyethylene chain length being balancedto pro? vide" good' detergency, a wetting agent selectedfro'mlthe group consisting of salts of organic sulfates and organic sulfonates and a calcium chelating agentvvhich' is an alkali metal salt of an amino acetic acid, said detergent, wetting agent and chelating agent being present respec tively in the following proportions by weight on. basis: 70-90%; 0:55%; and 5l5%.
5. A germicidal concentrate consisting essentially of a compatible solution in water of polyoxyethylenefnonyl phenol containing an average of 10 oxyethylen'e groups per mol, ethylene diamine-tetra-aceti'c acid sodiurni salt, and sodium dioctyl sulfosuccinatc, in the proportions on a dry basis of from 70 to of said polyoxyethylene nonyl phenol, from 5 to 15 of said ethylene diamine tetra-acetic acid sodium'salt, and from 0.5 to 5% of said sulfosuccinate. 3 H I I 6. A germicidal concentrate consisting of an aqueous solution of polyoxyethylenenonyl phenol containing an average of 10 oxyethylene groups per mol, sodiumdioctyl sulfosuccinate, and ethylene diamine tetra-acetic acidv tetra-spdipm salt, in substantially the proportions (dry basis) 84.4% polyoxyethylene nonyl phenol, 1.2% sulfosuccinate, 14.4% tetra-acetic acid salt.
References Cited in the file of this patent UNITED STATES PATENTS Crossley Feb. 28, 1939 Steindorfl et a1 Sept. 3, 1940 Bersworth Dec. 24, 1946 Lambert Dec. 11, 1951 Jenkens Apr. 17, 1956 10 6 OTHER REFERENCES