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

COMPOSITIONS D'ESTERS D'ACIDE P-HYDROXYBENZOIQUE; PREPARATION ET APPLICATIONS

English 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.

Claims

19
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.

21
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

22
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.

23
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.

24
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.


26
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.

27
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.

28
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.

29
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.

31
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.

32
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.

Description

1 177756




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
;

1 177756




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

1 177756


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.

1 177756




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).

1 177756


(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:

aclern~rK

7756

C~ 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 n ~n o o o o o o o o u~ o o In
,, ~ ~ ~ ~ ~ ~ ~ , ~ ~ ~ ~ ~
. o
U ++++++++++++++++++++
+ + -~ + + + ~ + + + + + + + + + + + + +

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

U~
~ +++++~++++++++++++++
- ~:
~ 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 ~
~ U o u~ o u~
u~ E~ ~ o ~ o~
O 1'~) 0
U~ ~ ~ U U U ~ ~ U 0
U U U U ~ ~ E~ Q)
~D U ~ ~ U ~D ~ U E~ D ~ V
E~ ) U a " ~¢ ~'1 0 C) ~ '1
U f~ 0 U E~
U U~ U ~ 0 U~ U 0 U ~: O
E~ Ql ~ U 115 ~ U O O O O O
w a1 C C ~ C Ll E~
0 ~ o 0 a.~ t~ t~ ) ~ ~ 1~
,a ~ o mo o ~ v 0
~1 0 0 o a) R. L~ a) c.~ al ~ aJ a~ JJ r~ -- .C
- E~ v ~ 0 ~ c ~ a m c.) m c ~
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~
O ~ ~ C ~0 .~ QO Oe o o Oe Eo~ O
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~

12
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~
dP
o

a v
N ~1 o Ut U~ 0 N 0 ~ O o ~ ~ ~ ~D
~ D W
X O A ~ A A
O U~
~ ~ ~1
al ~ v

, o~P
O
O
i~ V :~
~ ~ V
N 3 o o o o o u~ o o o o o o o ~ ~ n
u n ~ ~ ~ u~ o rJ o o o o o o o ~ ~ c~
_ ~ x o ~A A A A A
C V~ U~
O :1 ~ Ll
v o m v
~ W
'Sc
H
O O
C O
'V V~
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
~ D ~ O
OD U C~ '~
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~

1177756
14
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:

~17775~

oooooooooooooooo~o~
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~
) ~ ~ ~ ~ o a~
~ c O
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,) ~
. ~ al ~ 0 ~ c u~ c) 4
~: m u~ W c~ w p~ o, v v~

1 17~75~
16
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~
17

n o o o o o o o o o o o o o u~ ~ o n
U~ 7 0 U~ O O O O O O ~ r~
~ ~ ~ ~ O ~ ~ ~ ~ In o~ o~ o ~ ~ ~ ~ V

. o
+ + + + + + + + + + + + + + + + + + +
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
~ .
~J ~ ~ o
o 1` er a~ CO
~ C) o U~ o U~
u~ E~ ~ o r~
~D ~ CD cn o ~ ~)
E~ O Q
~ e s
E~ ) Q) O O O -~
0 :~ ~ a) 0 0 Q) 1~ N ~-1 Ll 0
~ q O O ~ ~ a) Oa~ ~ a) ~ ~ ~ r E~
1~ .~ U 0 C,) 0 C: V
Q C~ O
~: ~o o o u ~ ~ ~ 3
nl U U O 5
~ ~O U ~ U U ~ _1 ~ ~ O O O O O ,1
Ll ~ ~l ~1 U ~ ~ a~ cq ~ n E~
O ~1 ~ ~ ~ O O O O O ~ i~ ~ --I O
O _I .C .C P- O ~ ~ ~ ~ ~ ~ ~ ~ '~ ~ ~ C~ ''
~ ~ aJ .C D E~ IJ L~ n U a) ~r1 U
U U ~ ~ ~ U aJ ~ O ~ ~ ~ ~ ~ ~ t: U ~ ~

1 177756
18
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.