CA1177756A - Compositions of p-hydroxybenzoic acid esters and methods of preparation and use - Google Patents

Abstract

COMPOSITIONS OF p-HYDROXYBENZOIC ACID ESTERS
AND METHODS OF PREPARATION AND USE

Abstract of the Disclosure A composition having broad spectrum antimicrob-ial activity and being freeze and heat stable is com-prised of a clear solution containing up to approximately 90% by weight of a eutectic mixture of three or more lower alkyl esters of p-hydroxybenzoic acid such as iso-propyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate and n-butyl p-hydroxybenzoate in a ratio between approximate-ly 1:1:1 to 4:2:2, respectively, approximately 10% to 90%
by weight of a "Glydant" solution (composed of 55%
1,3-bis(hydroxymethyl)- 5,5-dimethylhydantoin and 45%
water) and at least approximately 0.5% by weight based on the weight of the eutectic mixture and the "Glydant"
solution of an anionic surfactant. The latter, for exam-ple, may be dioctyl sodium sulfosuccinate, sodium lauryl sulfate or the ammonium or sodium salt of sulfated nonyl-phenoxypoly(ethyleneoxy) ethanol.

Description

COMPOSITIO~S OF p-HYDROXYBENZOIC ACID ESTERS
AND METHODS OF PREPARATION AND USE

Background of the Inventio~
This invention relates to compositions useful in effecting antimicrobial activity against various microorganisms and, more particularly, to novel composi-tions containing lower alkyl esters of p-hydroxybenzoic acid and which are in the form of clear solutions which exhibit advantageous properties and to methods of prepar-ing and using such compositions.
~eretofore, it has been known that certain p-hydroxybenzoic acid alkyl esters such as isopropyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate and n-butyl p-hydroxybenzoate are useful as antimicrobial agents or preservatives. Such p-hydroxybenzoic acid esters are usually solid at room temperature and have generally ~een used as crystals in the United States. Ueno U.S. patent No. 3,097,131 does disclose that eutectic mixtures of p-hydroxybenzoic acid alkyl esters may be emulsified in an aqueous solution containing such colloid protecting substances as gelatin, carboxymethyl cellulose and the like. However, it is not believed that such emulsions have the desired degree of heat sta~ility or freeze sta-bility for all applications and also may be subject to "breaking" or separating into two phases. Accordingly, it would be advantageous to formulate p-hydroxybenzoic acid alkyl esters into clear solutions which are both heat and freeze stable without the necessity of employing a stabilizing agent.
Summary of the Invention Among the several objects of the invention may be noted the provision of novel compositions of lower alkyl esters of p-hydroxybenzoic acid exhibiting broad ;

spectrum antimicrobial activity; the provision of such compositions in the form of clear, colorless solutions;
the provision of compositions of this type which remain li~uid at temperatures down to -20C and are freeze and heat stable to 50C; and the provision of methods of pre-paring and using such compositions. Other objects and features will be in part apparent and in part pointed out hereinafter.
Briefly, the invention is directed to a com-position having broad spectrum antimicrobial activity which comprises a clear solution containing up to approx-imately 90~ by weight of a eutectic mixture of three or more lower alkyl esters of p-hydroxybenzoic acid, approx-imately 10% to 90% by weight of a solution containing approximately 55% of 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin and 45% of water, and at least approximately 0.5% by weight based on the weight of the eutectic mix-ture and the 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solution of an anionic surfactant. The invention is also directed to the method of preparing such compositions and to the method of using such compositions to effect anti-microbial activity against a microorganism.
Description of the Preferred Embodiments In accordance with the present invention, it has now been found that when a liquid eutectic mixture of three or more lower alkyl esters of p-hydroxybenzoic acid such as, for example, isopropyl p-hydroxybenzoate, iso-butyl p-hydroxybenzoate and n-butyl p-hydroxybenzoate, is mixed with a solution containing approximately 55% of 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin and 45% of water in the presence of an anionic surfactant, no emul-sion is formed but unexpectedly a clear, colorless solu-tion or composition is formed which exhibits advantageous properties. Thus, we have found that such compositions 1 1~77~

do not freeze but remain liquid at temperatures down to -20C and are both freeze and heat stable (e.g., at 50C). In addition, these compositions are economical to prepare and use and are compatible with most formulations into which they are incorporated. Further, they exhibit broad spectrum antimicrobial activity against various microorganisms.
It is believed that the clear solutions or compositi,ons of the inven-tion are in the form of microemulsions which exhibit stability without containing a stabilizing agent.
The eutectic mixtures whieh are a component of our novel compositions are in the form of oils and are composed of three or more lower alkyl esters (i.e., alkyl groups containing 1 to 6 carbon a-toms) of p-hydroxybenzoic acid such as isopropyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate and n-butyl p-hydroxy-benzoate in a ratio between approximately 1:1:1 and 4:2:2, preferably between 4:2.5:2.5 and 4:3:3. It will be understood that other eutectic mixtures of three or more lower alkyl esters of p-hydroxybenzoic acid such as a mix-ture of isopro-pyl p-hydroxybenzoate, sec-butyl p-hydroxybenzoate and amyl p-hydroxybenzoate, see-butyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate and n-butyl p-hydroxyben-zoate, ete. may likewise be used in the praetiee of the invention. Sueh euteetie mixtures are formed in _itu preferably by first reaeting .

I $7~75~

p-hydroxybenzoic acid and a lower alkanol such as isopro-pyl alcohol in the presence of an esterification catalyst such as sulfuric acid to form a first lower alkyl ester of p-hydroxybenzoic acid (e.g., isopropyl p-hydroxybenzo-ate), reacting the resulting mixture with two or more lower alkanols (e.g., isobutyl alcohol and n-butyl alco-hol) under heat to form a mixture of three or more lower alkyl esters of p-hydroxybenzoic acid (e.g., isopropyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate and n-butyl p-hydroxybenzoate), quenching the reaction when the ratio of the respective lower alkyl esters of p-hydroxybenzoic acid to each other is such that the mixture thereof is liquid at room temperature, and isolating the resulting eutectic mixture. These eutectic mixtures are thus formed directly without the necessity of forming and isolating the individual esters separately and then melting or otherwise blending them together to form liquid eutectic mixtures.
The second component of our novel compositions is a solution composed of 55% of 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin and 45~ of water marketed under the trade designation "Glydant"* by Glyco Chemicals, Inc.
This product as marketed is a clear solution having a pH
at 25C of 6.5-7.5 and a specific gravity of 1.1579 +
0.0026. It freezes at -20C.
The anionic surfactants which, in combination with the "Glydant"* solution, have been found useful to solubilize or microemulsify the above-referred-to eutec-tic oils or mixtures may be any suitable anionic surfac-tant such as, for example, dioctyl sodium sulfosuccinate, sodium lauryl sulfate and the ammonium or sodium salt of sulfated nonylphenoxypoly(ethyleneoxy) ethanol. The lat-ter may be the ammonium salt of sulfated nonylphenoxy-*Trademark r poly(ethyleneoxy) ethanol marketed under the trade desig-nations "Alipal~CO-436", "Alipal~EP-llO", "Alipal EP-115"
or "Alipal EP-120" or the sodium salt of sulfated nonyl-phenoxypoly(ethyleneoxy) ethanol marketed under the trade designation 'lAlipaL~co-433ll~ all by GAF Corporation.
Other anionic surfactants known to the art may also be used.
The amount of the eutectic oil or eutectic mix-ture which can be incorporated or solubilized into the compositions of the invention is dependent in part on which anionic surfactant is employed as well as on the amount of "Glydant" solution utilized. In general, up to approximately 90% by weight of the eutectic mixture may be solubilized in accordance with the practice of the in-vention using from approximately 10% to 90% by weight of the "Glydant" solution and at least 0.5% by weight of the anionic surfactant based on the weight of the eutectic mixture and the "Glydant" solution. More specifically, for example, approximately 90% of the eutectic mixture may be solubilized or microemulsified using 10% by weight of the "Glydant" solution and 6% by weight of dioctyl sodium sulfosuccinate based on the weight of the eutectic mixture and the "Glydant" solution, approximately 55% by weight of the eutectic mixture may be solubilized or microemulsified using 45% by weight of the "Glydant"
solution and 7% by weight of sodium lauryl sulfate based on the weight of the eutectic mixture and the "Glydant"
solution, and 40% by weight of the eutectic mixture may be solubilized or microemulsified using 60% by weight of the "Glydant" solution and 5% by weight of the ammonium salt of sulfated nonylphenoxypoly(ethyleneoxy) ethanol tmarketed under the trade designation "Alipal C0-436") based on the weight of the eutectic mixture and the "Glydant" solution. In each instance, if it is desired tra le ~ r ~

1 17775~

to incorporate lesser amounts of the eutectic mixture, smaller amounts of the "Glydant" solution and the respec~
tive anionic surfactants are required. In most in-stances, approximately 2% to 10~ by weight of the anionic surfactant component based on the weight of the eutectic mixture and the "Glydant" solution are used. Higher amounts of the anionic surfactant may be employed but are generally unnecessary.
- As stated, the clear solutions or microemul-sions of the invention possess broad spectrum antimicro-bial activity and are effective against various microor-ganisms including bacteria, yeast and fungi as illustrat-ed by the working examples set forth hereinafter. More-over, as shown, the compositions of the invention are effective at concentrations as low as 32 ppm.
The following examples further illustrate the practice of the invention.
Example 1 5 g of a eutectic mixture consisting of isopro-pyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate and n-butyl p-hydroxybenzoate in a ratio of 4:2.3:2.4 was placed in a small test tube and heated to 70C. 38.9 g of a solution marketed under the trade designation "Glydant" by Glyco Chemicals, Inc. (which is a solution composed of 55% 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin and 45% water) were added to a 150-ml beaker con-taining 1 9 of the ammonium salt of sulfonated nonylphe-noxypoly(ethyleneoxy) ethanol marketed under the trade designation "Alipal C0-436" by GAF Corporation, mixed and heated to 45C in a water bath. The two solutions were added together and the resulting mixture was a clear, colorless solution which did not freeze at -20C. The mixture remained stable at various temperatures. The mixture as constituted contained 11.1% by weight of the 1 1777~6 eutectic mixture and 86.6% by weight of the "Glydant"
solution with the "Alipal C0-436" constituting 2.2% by weight based on the weight of the eutectic mlxture and the "Glydant" solution.
Example 2 Example l was repeated without using the anion-ic surfactant "Alipal C0-436". The resulting mixture was an opaque mixture with an oil layer at the top.
- Example 3 Example l was repeated using 9.3% sodium lauryl sulfate (marketed under the trade designation "Duponol C") instead of 2.2% "Alipal C0-436". This produced a clear, slightly yellow solution.
Example 4 Example 3 was repeated using 2.2% sodium lauryl sulfate instead of 9.3%. This produced a clear solution.
Example 5 Example l was repeated using 2.2% dioctyl sodium sulfosuccinate instead of 2.2% "Alipal C0-436".
This produced a clear solution.
Example 6 34.5 g of the "Glydant" solution ~55% 1,3-bis-(hydroxymethyl)-5,5-dimethylhydantoin) was placed in a 150-ml beaker containing 2.2% of the anionic surfactant "Alipal C0-436". The resulting mixture was heated to ap-proximately 45C in a water bath and mixed well. 10 g of the eutectic mixture used in Example 1 was placed in a small test tube and heated to approximately 70C in a water bath. While the "Glydant"-"Alipal C0-436" mixture was being mixed on a magnetic stir plate, the eutectic mixture was added and the resultant mixture was further mixed for approximately 15 minutes. The resulting mix-ture was a clear solution.
i I 1 ~775~

Example 7 Example 6 was repeated using 25.9 9 of the "Glydant" solution, 2.1% dioctyl sodium sulfosuccinate and 20 g of the eutectic mixture. The resultant mixture was a clear solution.
Example 8 Example 6 was repeated using 21.6 g of the "Glydant" solution, 2.1% dioctyl sodium sulfosuccinate and 25 9 of the eutectic mixture. The resultant mixture was cloudy and yellowish in color. While mixing this mixture on a magnetic stir plate, an additional 2.1%
dioctyl sodium sulfosuccinate was added making a total of 4.2% dioctyl sodium sulfosuccinate based upon the weight of the "Glydant" solution and the eutectic mixture. The resulting mixture was a clear solution.
Example 9 Example 7 was repeated using 25.9 g water in-stead of 25.9 g of the "Glydant" solution. The resultant mixture was a white emulsion that split into two layers immediately.
Example 10 Example 8 was repeated using 2.1% sodium lauryl sulfate instead of 2.1% dioctyl sodium sulfosuccinate.
The resultant. mixture was cloudy and yellowish in color.
Upon the addition of another 2.1% sodium lauryl sulfate, a clear solution was obtained.
Example 11 Example 6 was repeated using 4.3 g of the "Glydant" solution, 45 g of the eutectic mixture and 5.7%
dioctyl sodium sulfosuccinate. A clear solution was formed.
Example 12 Example 6 was repeated using 19.4 g of the "Glydant" solution, 27.5 g of the eutectic mixture and 6.9% sodium lauryl sulfate. A clear solution was formed.

Example 13 Example 6 was repeated using 25.9 g of the "Glydant" solution, 20 g of the eutectic mixture and 5.1%
"Alipal C0-436". A clear solution was formed.
Example 14 The mixture or composition prepared as in Ex-ample 1 was tested to determine the minimum inhibitory concentration (MIC) of the composition against various microorganisms (i.e., bacteria, yeast and fungi~ accord-ing to the following procedure:
(A) Agar plate preparation (1) Tryptic Soy Agar (TSA) was prepared according to the manufacturer's directions by suspending 40 g TSA in cold deionized water (1 liter).
The suspension was heated to boiling in order to dissolve completely and then autoclaved for 15 minutes at 15 pounds pressure at 121C.

(2) After autoclaving, the media was cooled to 45C
in a water bath.

(3) At this point, the mixture was aseptically added to the TSA at different levels in order to obtain the desired test concentrations.
(B) Inoculum (1) The bacteria and yeast inoculum consisted of 0.1 ml of a 1:100 saline dilution of an over-night TSBIbroth culture (~ 106-107 CFU/ml).
CFU = Colony Forming Units.

(2) The fungus inoculum consisted of 0.1 ml of a spore-saline suspension harvested by gently rubbing the spores from a l-week old Sabourand dextrose agar slant incubated at 25C with sterile saline (~ 106-107 CFU/ml).

(3) A sterile Dacron swab was used to spread the inoculum evenly over the entire agar surface.

~C) Incubation (1) The bacteria and yeast plates were incubated at 35C for 48 hours.

(2) The fungus plates were incubated at 30C for - 72-96 hours.

(D) Recording of Results 0 = no grow,h 1+ = scant growth 2+ = moderate growth 3+ = heavy growth

4+ = confluent growth (same as control containing no preservative or antimicrobial agent) The MIC is defined as the least concentration of the com position required to completely inhibit the growth of a microorganism.
The results were as follows:

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. o U ++++++++++++++++++++
+ + -~ + + + ~ + + + + + + + + + + + + +

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~ +++++~++++++++++++++
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~ o P. U~ ++~+++++++++++++++++
o o ~ r + ~ o o ~ + + + + + + + o + + o o o + + + ~ +
o o o o ~ o o o o o o _l o o ~ o ~r o ~ o o o o o o o o o o o o o o o o o o o o o o o o o oooooooooooooooooooo ~ I O
a~ U CO ~ O ~
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U U~ U ~ 0 U~ U 0 U ~: O
E~ Ql ~ U 115 ~ U O O O O O
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,a ~ o mo o ~ v 0 ~1 0 0 o a) R. L~ a) c.~ al ~ aJ a~ JJ r~ -- .C
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0 ~ O c~ ~ c c 0 0 c, ~a ~ e ~ 0 m 0 0 .0 m e o ~o) g c) o 1 ~ ~a v 8 o o o o ~ o~
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O ~ s ~ R. ~ 0 0 C
t) ~ ~ ~ ~ u a) ~ o ~ ~ a~ ~ C
.. ~ ~ v v ~ m ,~ ~a ~ c) C m m m m m ~ ~ m c ~ 3 P. t4 ~ P. ~ U u~ ~: P. E~

1 17775~

The minimum inhibitory concentration for the "Glydant" per se is as follows:

Microorganism MIC (ppm) Bacillus subtilis ATCC 6633 500 Staphylococcus aureus ATCC 6538 500 Staphylococcus epidermidis ATCC 1228 500 Streptococcus faecalis 500 Escherichia coli ATCC 8739 500 Klebsiella pneumoniae ATCC 8308 500 Salmonella typhosa ATCC 6539250 Proteus vulgaris ATCC 13315 250 Serratia marcescens ATCC 8100500 Enterobacter cloacae ATCC 23355 500 Pseudomonas aeruginosa ATCC 9027 500 Pseudomonas aeruginosa ATCC 15442 500 Pseudomonas aeruginosa ATCC 13388 500 Pseudomonas aeruginosa ATCC 14502 500 Pseudomonas stutzeri 500 Candida albicans ATCC 102316000 Saccharomyces cerevisiae 250 Aspe~gillus niger ATCC-9642 2000 Penicillium chrysogenum ATCC 9480 4000 Trichophyton mentagrophytes 125 . The minimum inhibitory concentrations for iso-propyl p-hydroxybenzoate per se, isobutyl p-hydroxy~en-zoate per se and n-butyl p-hydroxybenzoate per se are as follows:

1 17775~
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o a v N ~1 o Ut U~ 0 N 0 ~ O o ~ ~ ~ ~D
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X O A ~ A A
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C V~ U~
O :1 ~ Ll v o m v ~ W
'Sc H
O O
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V N ~1 O O O O O O O O O O O 1/~ ~ Ir) N r~l U _I ~, ,1 ~n ol u~ _( o r) O u~ o o O o o o o ~ ~
o :~ O o A A A
U o ~
8 D. ~ v W ~ ~

N
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OU~
o ~ U
7 U U ~ ~ ~ e U w e U~ u cl ~ u ~ ~ ~ w ~ ~ u -0 U c o C C C C ' U _ ~- ~ u ~S c ~ C u _ ~ ~ O ~

~e o u~ ~ o ~ v 0~ ~ ~ ~ c -~ W 10 0 ~ W U ~ ~ a~ ~ V ,a u ~ C e w ,VO ~ ~ ~ U ~ V~ 0 U 0 ~ 0 .a w u w c ~
:1 U U O ~ 11 W .a U 0~ E~ O
~a w UO u UO S ~a 0 ~ e Vu ~c c ~ c c ~ e ~ ~ V~
CJ ~ U U ~ ~ ~ O O O O O O --I ~ .C
O 1 ~ ~ V ~ ~ C :~ --V Q0 o o o eO O ~ O
O ~ SS~, SQ, D S D ~ a) 'a ~ ~ ~ 'O ~ ~ -- S U S
u la V v v V ,~ a~ VC ~ C.) Q. C _ m u~ w x u~ ~ cn ~ P P u v~

Example 15 Example 14 was repeated using .he final compo-sition as prepared in Example 8.
Upon addition of the composition to the test media, oil beads of the eutectic mixture were formed. As the test media was mixed, the oil beads were broken up into smaller ones. The test media was mixed for several minutes and poured into the plates just prior to solidi-fication. After the plates were poured, all plates in-lQ cluding the one containing a concentration of 3~ ppm had visible oil beads, with the amount present decreasing as the concentration decreased.
The results of the determination of MIC activi-ty are as follows:

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C) U) U) U~ U) o U~ o o O O O 0o Oo ~n~ ~D U~ V V

O
V ++++++++++++++++++++

~ +++++++++++~++++++

, ~ ~r ~ ~r ~r er ~r ~ ~ ~r ~r ~ ~r ~r er er ~r o ~r O o ~ + + + + + + + + + + + + + + + + +

o ~ ~ r ~ ~ o ~ o o U~ +++++++++++++++ t N ,~ r ~ ~ O O ~1 0 0 o + + + + + + + +
u~ O O O O ~ o o o ~ ~ ~ ~ r ~ o o o o o o o o o o o o o o o o + + o + o o o o o o o o o o o o o o o o o o o o o o o o o o o ~ ~ o~ ~ o o r~ ~ OD 0, a~
~ O o In o u~
u~ E~ ~ o ~ o~ ~ ~1 ~1 ~o ~ co a~ o n ~ ~ U C~
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E~ o o o o C C C C ~ E~ ~ .'C
U~ U ~ o ~ ~ C t) ~ o 3 ~ ~ e o ~n u, ~ v~ ~ ~ c ,~ D~ Lg O ~ QJ al a) V 1~ R
R ~ U O ~ v~ ~~U~ UC U
c ~o go v ~t 0 la :~ R v to ~ v ~ V C) O .~: ~ ~ ~ U ~: C C C C n1 R ~ ~
c~- ~q o o 5,) o ,~ a o o o o o o ~1 ~I s ~ ~ ~1 _I O ~ O Q~ ~7 ~ R R R E R R ~
Q ~ C :~ v o O O O O O ~ ~ ~ ~ O
v ~ cc Q E v ~ Q~ a ~ r U S
u u ~ a ~ u al _I o ~ V ~ a) ~ c~ ~ c t,) ~
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1 17~75~

Example 16 Example 14 was repeated using the final compo-sition as prepared in Example 8 containing 10% dioctylsodium sulfosuccinate based upon the weight of the ~Glydant" solution and the eutectic mixture.
Upon addition of the composition to the test media and pouring of the resultant mixture into the plates, oil beads were present in those plates containing a concentration of 2000, 1000 and 500 ppm. At concentra-tions below 500 ppm, oil beads were not visible to the naked eye.
The results of the determination of MIC activi-ty are as follows:

1 1~77~

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~ ~ ~ ~ O ~ ~ ~ ~ In o~ o~ o ~ ~ ~ ~ V

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o ~ ~ ~r ~ ~r ~ ~r ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ , C~
~ +++++++++++++++ ++
r~ ~ er ~ ~ er d' ~ ~ ~ r o ~ o . ~ + + + + + + + + + + + + + + + + +
~9 ~ ~ ~ ~ ~ ~ ~ ~ ~ r ~ ~ o ~ ~1 o ~ ~ +++++++++++++ +
~ ~ o ~ ,1 ~ ~r ~ ~ ~ ~ ~ ~ ~r ~ ~ o o ,1 o o ~ o o o + + + + + + +
O er o o o ~ ~ ~ ~r ~ ~ o o o o o o + + + + +
u~ o o o o ~ o o o ~ o ~ ~r ~ o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o ~ .
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U U ~ ~ ~ U aJ ~ O ~ ~ ~ ~ ~ ~ t: U ~ ~

Thus, the antimicrobial activity was greater than that of the composition tested in Example 15 since more of the eutectic oil solution was incorporated into the test media.
Example 17 Example 1 was repeated using 5 g of a eutectic mixture of isopropyl p-hydroxybenzoate, sec-butyl p-hy~
droxybenzoate and amyl p-hydroxybenzoate in a ratio of 4:1.8:4.8, 39 g of the "Glydant" solution and 1.7 9 (3.7%) of sodium lauryl sulfate. This produced a clear solution.
Example 18 Example 17 was repeated using 15 g of the eutectic mixture, 13 g of the "Glydant" solution and approximately 3 g (9.1~) of sodium lauryl sulfate. This produced a clear solution.
Example 19 Example 1 was repeated using 5 g of a eutectic mixture of sec-butyl p-hydroxybenzoate, isobutyl p-hy-droxybenzoate and n-~utyl p-hydroxybenzoate in a ratio of 2.3:4:2.83, 3g g of the "Glydant" solution and 1 9 (2.2%~
of sodium lauryl sulfate. This produced a clear solution.
Example 20 Example 19 was repeated using 25 9 of the eutectic mixture, 21.5 g of the "Glydant" solution and 5 g (9.7%) of sodium lauryl sulfate. This produced a clear solution.
In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained.
As many changes could be made in the above products and methods without departing from the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illus-trative and not in a limiting sense.

Claims (55)

Claims WHAT IS CLAIMED IS:

1. A composition having broad spectrum antimi-crobial activity comprising a clear solution containing up to approximately 90% by weight of a eutectic mixture of three or more lower alkyl esters of p-hydroxybenzoic acid, approximately 10% to 90% by weight of a solution containing 55% of 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin and 45% of water, and at least approximately 0.5% by weight based on the weight of said eutectic mix-ture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution of an anionic surfactant.

2. A composition as set forth in claim 1 wherein said anionic surfactant is selected from the group consisting of dioctyl sodium sulfosuccinate, sodium lauryl sulfate and the ammonium or sodium salt of sul-fated nonylphenoxypoly(ethyleneoxy) ethanol.

3. A composition as set forth in claim 1 wherein said clear solution contains approximately 90% by weight of said eutectic mixture, approximately 10% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution and approximately 6% by weight of dioctyl sodium sulfosuccinate based on the weight of said eutec-tic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethyl hydantoin solution.

4. A composition as set forth in claim 1 wherein said clear solution contains approximately 55% by weight of said eutectic mixture, approximately 45% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution and approximately 7% by weight of sodium lauryl sulfate based on the weight of said eutectic mix-ture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution.

5. A composition as set forth in claim 1 wherein said clear solution contains approximately 50% by weight of said eutectic mixture, approximately 50% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethyihydan-toin solution and approximately 10% by weight of dioctyl sodium sulfosuccinate based on the weight of said eutec-tic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin solution.

6. A composition as set forth in claim 1 wherein said clear solution contains approximately 40% by weight of said eutectic mixture, approximately 60% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution and approximately 5% by weight of the ammonium salt of sulfated nonylphenoxypoly(ethyleneoxy) ethanol based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solution

7. A composition as set forth in claim 1 wherein said clear solution contains approximately 10% by weight of said eutectic mixture, approximately 90% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution and approximately 2% by weight of the ammonium salt of sulfated nonylphenoxypoly(ethyleneoxy) ethanol based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion.

8. A composition as set forth in claim 1 wherein said clear solution contains between approximate-ly 2% and 10% by weight of said anionic surfactant based on the weight of said eutectic mixture and said 1,3-bis-(hydroxymethyl)-5,5-dimethylhydantoin solution.

9. A composition having broad spectrum antimi-crobial activity comprising a clear solution containing up to approximately 90% by weight of a eutectic mixture of isopropyl p-hydroxybenzoate, isobutyl p-hydroxybenzo-ate and n-butyl p-hydroxybenzoate in a ratio between ap-proximately 1:1:1 and 4:2:2, respectively, approximately 10% to 90% by weight of a solution containing approxi-mately 55% of 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin and 45% of water, and at least approximately 0.5% by weight based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion of an anionic surfactant.

10. A composition as set forth in claim 9 wherein said anionic surfactant is selected from the group consisting of dioctyl sodium sulfosuccinate, sodium lauryl sulfate and the ammonium or sodium salt of sul-fated nonylphenoxypoly(ethyleneoxy) ethanol.

11. A composition as set forth in claim 9 wherein said eutectic mixture of isopropyl p-hydroxyben-zoate, isobutyl p-hydroxybenzoate and n-butyl p-hydroxy-benzoate has a ratio of 4:2.5:2.5, respectively.

12. A composition as set forth in claim 9 wherein said clear solution contains approximately 90% by weight of said eutectic mixture, approximately 10% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution and approximately 6% by weight of dioctyl sodium sulfosuccinate based on the weight of said eutec-tic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin solution.

13. A composition as set forth in claim 9 wherein said clear solution contains approximately 55% by weight of said eutectic mixture, approximately 45% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution and approximately 7% by weight of sodium lauryl sulfate based on the weight of said eutectic mix-ture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution.

14. A composition as set forth in claim 9 wherein said clear solution contains approximately 50% by weight of said eutectic mixture, approximately 50% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin solution and approximately 10% by weight of dioctyl sodium sulfosuccinate based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solution.

15. A composition as set forth in claim 9 wherein said clear solution contains approximately 40% by weight of said eutectic mixture, approximately 60% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin solution and approximately 5% by weight of the ammonium salt of sulfated nonylphenoxypoly(ethyleneoxy) ethanol based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solution.

16. A composition as set forth in claim 9 wherein said clear solution contains approximately 10% by weight of said eutectic mixture, approximately 90% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin solution and approximately 2% by weight of the ammonium salt of sulfated nonylphenoxypoly(ethyleneoxy) ethanol based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solution.

17. A composition as set forth in claim 9 wherein said clear solution contains between approximate-ly 2% and 10% by weight of said anionic surfactant based on the weight of said eutectic mixture and said l,3-bis-(hydroxymethyl)-5,5-dimethylhydantoin solution.

18. The method of preparing a composition having broad spectrum antimicrobial activity comprising mixing up to 90% by weight of a eutectic mixture of three or more lower alkyl esters of p-hydroxybenzoic acid with approximately 10% to 90% by weight of a solution contain-ing approximately 55% of 1,3-bis(hydroxymethyl)-5,5-di-methylhydantoin and 45% of water and at least 0.5% by weight based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion of an anionic surfactant to produce a clear solution having broad spectrum antimicrobial activity.

19. The method as set forth in claim 18 wherein said anionic surfactant is selected from the group consisting of dioctyl sodium sulfosuccinate, sodium lauryl sulfate and the ammonium or sodium salt of sul-fated nonylphenoxypoly(ethyleneoxy) ethanol.

20. The method as set forth in claim 18 wherein said clear solution contains approximately 90% by weight of said eutectic mixture, approximately 10% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution and approximately 6% by weight of dioctyl sodium sulfosuccinate based on the weight of said eutec-tic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin solution.

21. The method as set forth in claim 18 wherein said clear solution contains approximately 55% by weight of said eutectic mixture, approximately 45% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin and approximately 7% by weight of sodium lauryl sul-fate based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)- 5,5-dimethylhydantoin solu-tion.

22. The method as set forth in claim 18 wherein said clear solution contains approximately 50% by weight of said eutectic mixture, approximately 50% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin and approximately 10% by weight of dioctyl sodium sulfosuccinate based on the weight of said eutectic mix-ture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution.

23. The method as set forth in claim 18 wherein said clear solution contains approximately 40% by weight of said eutectic mixture, approximately 60% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin and approximately 5% by weight of the ammonium salt of sulfated nonylphenoxypoly(ethyleneoxy) ethanol based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solution.

24. The method as set forth in claim 18 wherein said clear solution contains approximately 10% by weight of said eutectic mixture, approximately 90% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin and approximately 2% by weight of the ammonium salt of sulfated nonylphenoxypoly(ethylenoxy) ethanol based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solution.

25. The method as set forth in claim 18 wherein said clear solution contains between approxi-mately 2% and 10% by weight of said anionic surfactant based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solution.

26. The method as set forth in claim 18 wherein said eutectic mixture and a mixture of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin and said anionic surfactant are heated prior to being mixed together.

27. The method of preparing a composition having broad spectrum antimicrobial activity comprising mixing up to 90% by weight of a eutectic mixture of isopropyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate and n-butyl p-hydroxybenzoate in a ratio between ap-proximately 1:1:1 and 4:2:2, respectively, with approxi-mately 10% to 90% by weight of a solution containing approximately 55% of 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin and 45% of water and at least 0.5% by weight based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solution of an anionic surfactant to produce a clear solution having broad spectrum antimicrobial activity.

28. The method as set forth in claim 27 wherein said anionic surfactant is selected from the group consisting of dioctyl sodium sulfosuccinate, sodium lauryl sulfate and the ammonium or sodium salt of sul-fated nonylphenoxypoly(ethyleneoxy) ethanol.

29. The method as set forth in claim 27 wherein the eutectic mixture in said composition is a mixture of isopropyl p-hydroxybenzoate, isobutyl p-hy-droxybenzoate and n-butyl p-hydroxybenzoate having a ratio of 4:2.5:2.5, respectively.

30. The method as set forth in claim 27 wherein said clear solution contains approximately 90% by weight of said eutectic mixture, approximately 10% by weight of said l,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution and approximately 6% by weight of dioctyl sodium s,ulfosuccinate based on the weight of said eutec-tic mixture and said l,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin solution.

31. The method as set forth in claim 27 wherein said clear solution contains approximately 55% by weight of said eutectic mixture, approximately 45% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution and approximately 7% by weight of sodium lauryl sulfate based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhy-dantoin solution.

32. The method as set forth in claim 27 wherein said clear solution contains approximately 50% by weight of said eutectic mixture, approximately 50% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution and approximately 10% by weight of dioctyl sodium sulfosuccinate based on the weight of said eutec-tic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin solution.

33. The method as set forth in claim 27 wherein said clear solution contains approximately 40% by weight of said eutectic mixture, approximately 60% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin solution and approximately 5% by weight of the ammonium salt of sulfated nonylphenoxypoly(ethyleneoxy) ethanol based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solution.

34. The method as set forth in claim 27 wherein said clear solution contains approximately 10% by weight of said eutectic mixture, approximately 90% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin solution and approximately 2% by weight of the ammonium salt of sulfated nonylphenoxypoly(ethylenoxy) ethanol based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solution.

35. The method as set forth in claim 27 wherein said clear solution contains between approximate-ly 2% and 10% by weight of said anionic surfactant based on the weight of said eutectic mixture and said l,3-bis-(hydroxymethyl)-5,5-dimethylhydantoin solution.

36. The method as set forth in claim 27 wherein said eutectic mixture and a mixture of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solution and said anionic surfactant are heated prior to being mixed together.

37. A method of effecting antimicrobial activ-ity against a microorganism comprising contacting said microorganism with a composition comprising a clear solu-tion containing up to approximately 90% by weight of a eutectic mixture of three or more lower alkyl esters of p-hydroxybenzoic acid, approximately 10% to 90% by weight of a solution containing approximately 55% of 1,3-bis-(hydroxymethyl)-5,5-dimethylhydantoin and 45% of water, and at least approximately 0.5% by weight based on the weight of said eutectic mixture and said 1,3-bis(hydroxy-methyl)-5,5-dimethylhydantoin solution of an anionic sur-factant.

38. A method as set forth in claim 37 wherein said anionic surfactant is selected from the group con-sisting of dioctyl sodium sulfosuccinate, sodium lauryl sulfate and the ammonium or sodium salt of sulfated nonylphenoxypoly(ethyleneoxy) ethanol.

39. A method as set forth in claim 37 wherein said clear solution contains approximately 90% by weight of said eutectic mixture, approximately 10% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion and approximately 6% by weight of dioctyl sodium sulfosuccinate based on the weight of said eutectic mix-ture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution.

40. A method as set forth in claim 37 wherein said clear solution contains approximately 55% by weight of said eutectic mixture, approximately 45% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion and approximately 7% by weight of sodium lauryl sul-fate based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion.

41. A method as set forth in claim 39 wherein said clear solution contains approximately 50% by weight of said eutectic mixture, approximately 50% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion and approximately 10% by weight of dioctyl sodium sulfosuccinate based on the weight of said eutectic mix-ture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution.

42. A method as set forth in claim 39 wherein said clear solution contains approximately 40% by weight of said eutectic mixture, approximately 60% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion and approximately 5% by weight of the ammonium salt of sulfated nonylphenoxypolylethyleneoxy) ethanol based on the weight of said eutectic mixture and said 1,3-bis-(hydroxymethyl)-5,5-dimethylhydantoin solution.

43. A method as set forth in claim 37 wherein said clear solution contains approximately 10% by weight of said eutectic mixture, approximateiy 90% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion and approximately 2% by weight of the ammonium salt of sulfated nonylphenoxypoly(ethyleneoxy) ethanol based on the weight of said eutectic mixture and said l,3-bis-(hydroxymethyl)-5,5-dimethylhydantoin solution.

44. A method as set forth in claim 37 wherein said clear solution contains between approximately 2% and 10% by weight of said anionic surfactant based on the weight of said eutectic mixture and said 1,3-bis(hydroxy-methyl)-5,5-dimethylhydantoin solution.

45. A method as set forth in claim 37 wherein the minimum inhibitory concentration of said composition contacting said microorganism ranges between 32 ppm and 2000 ppm.

46. A method of effecting antimicrobial activ-ity against a microorganism comprising contacting said microorganism with a composition comprising a clear solu-tion containing up to approximately 90% by weight of a eutectic mixture of isopropyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate and n-butyl p-hydroxybenzoate in a ratio between approximately 1:1:1 and 4:2:2, respective-ly, approximately 10% to 90% by weight of a solution con-taining approximately 55% of 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin and 45% of water, and at least approxi-mately 0.5% by weight based on the weight of said eutec-tic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethyl-hydantoin solution of an anionic surfactant.

47. A method as set forth in claim 46 wherein said anionic surfactant is selected from the group con-sisting of dioctyl sodium sulfosuccinate, sodium lauryl sulfate and the ammonium or sodium salt of sulfated nonylphenoxypoly(ethyleneoxy) ethanol.

48. A method as set forth in claim 46 wherein said eutectic mixture of isopropyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate and n-butyl p-hydroxybenzoate has a ratio of 4:2.5:2.5, respectively.

49. A method as set forth in claim 46 wherein said clear solution contains approximately 90% by weight of said eutectic mixture, approximately 10% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion and approximately 6% by weight of dioctyl sodium sulfosuccinate based on the weight of said eutectic mix-ture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution.

50. A method as set forth in claim 46 wherein said clear solution contains approximately 55% by weight of said eutectic mixture, approximately 45% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion and approximately 7% by weight of sodium lauryl sul-fate based on the weight of said eutectic mixture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion.

51. A method as set forth in claim 46 wherein said clear solution contains approximately 50% by weight of said eutectic mixture, approximately 50% by weight of said l,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion and approximately 10% by weight of dioctyl sodium sulfosuccinate based on the weight of said eutectic mix-ture and said 1,3-bis(hydroxymethyl)-5,5-dimethylhydan-toin solution.

52. A method as set forth in claim 46 wherein said clear solution contains approximately 40% by weight of said eutectic mixture, approximately 60% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion and approximately 5% by weight of the ammonium salt of sulfated nonylphenoxypoly(ethyleneoxy) ethanol based on the weight of said eutectic mixture and said 1,3-bis-(hydroxymethyl)-5,5-dimethylhydantoin solution.

53. A method as set forth in claim 46 wherein said clear solution contains approximately 10% by weight of said eutectic mixture, approximately 90% by weight of said 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin solu-tion and approximately 2% by weight of the ammonium salt of sulfated nonylphenoxypoly(ethyleneoxy) ethanol based on the weight of said eutectic mixture and said l,3-bis-(hydroxymethyl)-5,5-dimethylhydantoin solution.

54. A method as set forth in claim 46 wherein said clear solution contains between approximately 2% and 10% by weight of said anionic surfactant based on the weight of said eutectic mixture and said 1,3-bis(hydroxy-methyl)-5,5-dimethylhydantoin solution.

55. A method as set forth in claim 46 wherein the minimum inhibitory concentration of said composition contacting said microorganism ranges between 32 ppm and 2000 ppm.