Note: Descriptions are shown in the official language in which they were submitted.
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The invention relates to antimicrobial-containing
resin composi-tions, and more particularly synthetic resin
compositions incorporating an aromatic derivative of a mono-
halogenated phenolic antimicrobial compound, whlch subsequent
to processing, exhibits a level of long._term persistent
antimicrobial activi-tyO
In recent years considerable effort has been
expended in attempting to develop biostatic-biocidal synthetic
1~ resin compositions wherein the antimicrobial activity of the
composition is not significantly affectèd by temperatures
and pressures normally encountered in the processing of the
compositions into a myriad of final products.
As those well versed in the art of antimicrobial
compounds are aware, it is well recognized that the bio-
~1 static~biocidal activity of closely related compounds
l generally varies consîderably. The variance in activi-ty is
generally not only unpredic-tabl~ with respect to the compounds
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per se, but is greatly magnified when such compounds are
incorporated in synthetic resin compositions ~hat require
the addition oP plasticizers, s-tabilizers, lubricants and
, pigments in order to render the resin suitable for processing
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i~ into final products.
Accordingly, the ~act that a glven compound has
per se recogniæed antimicrobial activity does not in fact
assure that such compound will have the same degree of, or
any, antimlcrobacterial actlvity when incorporated in other
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than an inert solvent-carrier. The class of biostats-biocides
comprising halogenated phenols is a prime example. While the
grea-ter germicidal activity of monohalogen substituted alkyl
derivatives of phenol over phenol was recognized in the early
l900's it was almost thirty years before some potent germi-
cidal compounds were discovered among the aromatic derivatives
of p-chlorophenol. Among these compounds was the benzyl
derivative which was tested against test organisms of the
typhoid colon group. The results proved promising and
10 eventually led to the commercial development of o-~enzyl-p~ ;
chlorophenol, a potent broad spectrum antimicrobial which in
non-aqueous solution has for many years been utilized for the
sanitizing of hard surEaces, laundering fabrics, and with
dispersing agents, compounded into aqueous detergent compositions
having high phenol coefficients.
Therefore, a substantial amount of experimentation
is more often than not involved in the development of bio-
static-biocidal resin compositions ~hat after processing
into a final product retain an effective level of antimicro-
bial activity over a period of time whereby such productsretain such activity during substantially the useful life of
the product. It will thus be appreciated that the mere fact
that a compound, per se, or in certain solvents or composi-
tions, has antimicrobial properties does not render such
comE~ound as an obvious antimicrobial additive for incorpora-
tion in synthetic resin compositions, particularly such
compositions that must be subjected to relatively high
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processing temperatures and pressures in order to produce a
final consumer product.
Prior art attempts to provide antimicrobial
synthetic resinous compositions, as distinguished from merely
precluding microbial degredation of polymeric compositions,
have often utilized organo-metallic compounds, particularly
those based on mercury, tin, arsenic, copper as the active
antimicrobial compound. Other classes of antimicrobial
compounds include brominated salicylanilides, mercaptans,
10 quaternary ammonium compounds and carbamates, for example~
Generally, the above-mentioned compounds are characterized
by serious drawbacks in that they are highly specific in
their antimicrobial activity, highly toxic, and thermally
degredated, whereby commercial utilization of such
compounds is not practical or advisable.
While it is appreciated that many polynters inherently
resist biological attack these polymers are seldom used
without modification. Other materials such as plasticizers,
stabilizers, lubricants, and fillers, necessary for providing
~0 resinous compositions that can be molded and extruded on a
commercial scale, increases the pol~ner's vulnerability to
fungi and bacteria since they act as a source of food fQr
microorganisms. :,,
Not the least of the problems associated wi~h the
molding and extruding of an an~imicrobial thermoplastic
composition is the provision of a composition capable of
withstanding molding and extruding temperatures in the order
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of 400 to 500F. Temperatures of this order are necessary for
the dispersion of the antimicrobial compound in a thermoplastic
synthetic resin, pelletizing of the antimicrobial resinous com-
position to facilitate handling for subsequent fusion of the
pelletized resinous composition to mold or extrude articles and/
or film from high molecular weight high density polyethylene,
polystyrene, polypropylene, and ilm grade polyvi~ylchloride
without significant degradation of the active antimicrobial com-
pound incorporated therein.
The present invention accordingly provides an antimi-
crobial composition comprising a synthetic resin or polymer and
an antimicrobially effective amount of ortho-benzyl-para-
chlorophenol.
The present invention also provides a method of pro-
ducing a polymeric article having antimicrobial properties, which
comprises moulding, at a temperature of about 275F. to about -
500F., a composition comprising a synthetic resin or polymer and
an antimicrobially effective amount of ortho-benzyl-para-
chlorophenol.
Compounding of the antimicrobial synthetic resinous
compositions of the present invention is generally by post poly-
merization addition of the crystalline ortho-benzyl-para-chloro-
phenol to a high molecular weight generally rigid polymer.
"
Alternatively dispersion of the antimicrobial compound may be
` effected by blending with the polymer which is heat~d to at least
above a second transition
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-tempera-ture. Still fur-ther~ -the antimicrobial compound may be
dispersed in the finished polymer as a solution oF the ortho-
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benzyl-para-chlorophenol in an or~anic solven-t, such as
dioctylphthalate. The invention also contemplates the dis-
persion of crys-talline ortho-benzyl-para-chlorophenol in a
particulate dlluen-t vehicle, such as a micropulverized
anhydrous sodium potassium aluminum silica-l:e prior to dis-
persion in a fused or par-ticulate resin.
It has been found that the invention is particularly
well suited for imparting antimicrobial properties to high
molecular weight polyethylene, of both low and high density,
regular grade polystyrene, high impact polystyrene, poly-
propylene, high temperature polypropylene, and film grade :~
polyvinylchloride, for example. The ortho-benzyl-para-
chlorophenol has been generally found to impart significant
persistent antibacterial, antifungal and antiprotozal
activity to articles and films molded and extruded from ~`
synthetic resinous compositions containing in the finished
products a minumum of about 0.25% to 0.50% by weight of the
active antimicrobial compounds. It will be appreciated tha-t
the ortho_benzyl_para-chlorophenol may belincorporated in the ~;
resin at a use concentration of about 0.25% to about 0.50%
by weight whereby the antimicrobial resinous composition,
which may include the usual fillers and plasticizers, may
be in appropriate particulate or pelletized form fed direc-tly
to conventional molding and extruding apparatus. As a
practical matter 7 it has been found advisable to :incorporate
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the antimicrobial ortho-ben~yl para~chlorophenol in resin at
a concentration generally in excess of the use concentra-tion
so that anti~icrobial compound loaded pellets or granules,
may be physically admixed with non-antimicrobial containing
resin to arrive at a finished molded or extruded product
having the required use concentrati.on of ortho-benzyl-para-
chlorophenol in resin intended ~or subsequent admixture with
other compatible resin prior to molding or extruding is in
the order of about 10% by weight. ~1hile the incorporation of
more than 10% might be advantageous, it has been found -that
problems of recrys-tallization of the ortho-benzyl-para-
chlorophenol are sometimes encountered. However, i-t will be
appreciated that the incorporation of greater~percentages of
the antlmicrobial composi-tion is contemplated by the present
invention, albeit necessarytto utilize a solvent or diluent
system, other than that speciflcally set forth herein, to
preclude recrystallization of -the ortho-benzyl-para-chloro-
phenol in the antimicrobial resinous composition o~ finished
molded or extruded product,
Antimicrobial resinous compositions formulated in
accordance with the present invention have been prepared
wherein the concentration of ortho-benzyl para-chlcrophenol
is in -the order of 0.25% to ln.0% by weight of the resin and
any resin processing adjuncts admixed therewith. ~t will be
; appreciated however that these concentrations of ortho-benzyl_ :
para-chlorophenol are preferred and the invention broadly
contemplates the inco~poration of any concentration of the
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compound that will provide an effective level of the anti-
microbial compound ortho-benzyl-para-chlorophenol in a molded
or extruded resinous product.
The following are examples of preferred modes of
carrying forth the present invention with a plurality of
polymers. The term polymer as used herein is intended to
include generally solid synthetic monopolymers, copolymers,
etc., which do not effect any signiEicant re-arran~ement of
the ortho-benzyl-para-chlorophenol to a related but less
effective compound, even though in a technical sense such
degredation product exhibits antimicrobial activity.
Example I
Hi~h Molecular Weight Low Density Polyethylene
0.25%, by weight, of crystalline ortho-benzyl-para-
chlorophenol was physically blended with th-e resin in
particulate form and fed into an extruder barrel maintained
at a feedstock end temperature of 250 to 250F and extruded
and cut to form molding pellets. The ortho-benzyl-para-
chlorophenol-polyethylene pellets were then molded into pill
cups, as utilized in hospitals, in conventional injection
- molding apparatus operating at a temperature of 280 to 320F.
Representative segments of the exterior and interior
sides of the molded cups were then subjected to bacterio-
logical testing as follows: ~
PROCEDURE: -
Test Sample:
The sample was tested using the exterior and
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interior sides randomly vs. each organism.
Test Media:
A.A.T.C.C. Bacteriostasis Agar
Test Or~anisms:
Staphylococcus aureus 6538
Escherichia coli 4352
Streptococcus faecalis 14506
TnCubation:
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24 hours at 37C
RESULTS: Zone o~ Inhibition in mm.
Organism 1 2 3 Av~.
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S. aureus 3.0 3.0 3.0 3.0
E. coll 6.0 5.0 5.0 5.3
S. aecalis 3.0 3.0 3.0 3.0
CONCLUSION: The data obtained indicates that the submitted
sample exhibits bacteriostatic properties against S. aureus,
E. coli, and S. aecalis when tested as specified~
Example II
; Example ~ was repeated with the exception that
10.0% by weight, of ortho-benzyl-para-chlorophenol was `
incorporated and the pellets so obtained admixed with high
molecular weight low density polyethylene pellets containing
no ortho-benzyl-para-chlorophenol to arrive at a blend con~ -
centration of 0.50% by weight, of the antimicrobial compound ~,r~
in finished articles molded from the composit~ion. The results
of bacteriological tests were substantially the same as with
respect to Example I~
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Example III
High Molecular Weiqht Hiqh Density Polye~lene
0.25%, by weight, of crystalline ortho-benzyl-para-
chlorophenol was physically blended with particulate film
grade high molecular weight high density polyethylene and
fed into an extruder barrel maintained at a feedstock end
temperature of 280 to 320F and extruded and cut to form
pellets. The pellets were fed to an extruder apparatus ~;;
operating at 480F and extruded into tubular stock which was
slit to form sheet material. In separate runs material of 1,
5 and 7 mils was extruded. Representative portions of the
film were sub~ected to bacteriological testing and found to
exhibit antimicrobial activity comparable to the samples of
Example I.
In addition, human patch tests and animal oral
toxicity tests were conducted as follows:
PROCEDURES:
A. Human Patch Test
'ren (10) test subjects, five (5) male and five (5) ~`
female were selected at random. A skin area on the inner
surface of the right forearm of each subject was designated
for the position of the patch. The sample of 3 cm2 was placed
, in direct contact-with the skin at the designated site of
application. The patch was then covered with a Pressoplast
"Schwartz" patch having a 1 ~/2" x 1 1/2" cellophane center -
to retard evaporation of any volatile constituents of the
test sample~ The patch remained in contact with the skin for
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a period of twenty-four (24) hours. Upon removal of the
patch the resulting reaction was evaluated. Read~ngs were
also made after 72 hours and the results were incorporated
into the final evaluation.
After a five (5) day rest period the ten (10) sub-
jects utilized in the first phase of the test program were
again exposed to the sample for twenty-four (2~) hours. The
procedure followed the pattern as descriibed in the first
phase of the test. A positive reaction in the second phase
and a negative reaction in the first indicate the presence
of sensitizing agents producing an allergic reaction.
B. Ac~lte oral Toxici~y
An aqueous extract of the submitted sample was
prepared by placing 100 gms of sample in 200 mls of distilled
water with a pH of 7 o rrhe closed glass container was then
placed in an oven maintained at 65C for seven (7) days.
Ten (1~) Sherman Strain albino rats (5 male and 5
female) each weighing between 200 gms and 250 gms were
` selected for the test. Prior to the administration of the ;
extract, the food was withheld from the rats for 24 hours.
The animals were then weighed and grouped according to the
dosage to be administered.
The extract was then fed to the rats by direct
stomach intubation using a syringe with a "ball-point" needle.
The-animals were retained in their individual wire mesh cages
in the conditioned animal room for observa~ions of overk
toxic manifestations for a period of fourteen ~14) days.
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Results:
A. Human Patch Test
Primary
Reaction Reaction Combined
Subject Sex 2~ hrs. 72 hrs. Avera~e
1 M 0 0 0
2 M 0 0 0
3 M 0 0 0
4 M 0 0 0
M 0 0 0
6 F 0 0 0
7 F 0 0 0
8 F 0 0 0 `
~ 9 F 0 0 0
- 10 F 0 0
Second r~
1 M 0 0 0
2 M 0 0
3 M 0 0 0
4 M 0 0 0
M 0 0 0 `
6 F 0 0 0
7 F 0 0 0
! 8 F 0 0 0
. 9 F O O O
F O O O
B. Acute Oral Toxicit~ -
Dosage per K~ Mortality
of Body Wei~ht Ratio _
25 mils 0/10
observation: -
The animals in acute oral toxicity test showed no
overt toxic effect during the observation period.
Example IV
Example III was repeated with the exception that
the concentration of ortho-benzyl-para-chlorophenol incorpo-
rated in the high density polyethylene was increased to 10.0%
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and the antimicrobial containing pellets admixed with high
density polyethylene pellets to provide a finished film
havin~ 0.50% by weight of ortho-benzyl-para-chlorophenolO
The film was subjected to backerologixal testing and found to
have antimicrobial activity comparable to the composition
of Example II.
Example V
Example IV was repeated with the exception that
about 25% by weight of a micropulverized complex of silicates,
namely anhydrous sodium potassium aluminum silicate was
admixed with the ortho-ben~yl-para-chlorophenol as an inert
diluent to assist in uniformly dispersing the antimicrobial
comp~und throughout the resin matrix. The film was subjected
to bacteriological testing and found to have antimicrobial
activity comparable to the composition o~ Example IV.
Example VI
An intimate admixture of particulate polystyrene
with 0.25%, by weight, of ortho-benzyl-para-chlorophenol was
int~roduced into an extruder barrel wherein the ~eedstoc~ end
of the extruder barrel was maintained at a temperature in the
range of 265 to 420F and the antimicrobial polystyrene
extruded and chopped into molding pellets. The pellets were
then fed to an injection molding apparatus operating at a
temperature in the range of 4~0F and pill cups molded from -
the composition. Results of tests for antibacterial activity
were comparable to the results set forth with regard to
Example I.
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Example VII
Example VI was repeated with the exception that
high impact polystyrene, i.e., which contains butadiene
copolymer was substituted for regular grade polystyrene.
Example VIII
Example VII was repeated with the exception that ~
10.0%, by weight, of crystalline ortho-benzyl-para-chloro- ~ ~-
phenol was dissolved in dioctyl phthalate and the solution of
the antimicrobial compound incorpor,ated in the high impact
polystyrene heated to a temperature in the order of 375F.
Example X
Polypropylene, of a molecular weight in excess of
40,000 was heated in an extruder barrel maintained at a
temperature in the range of 275 to 325F at the ~eedstock
end and 0.25% by weight, of ortho-benzyl-para-chlorophenol
incorporated therein, the extruded antimicrobial composition
chopped into pellets. Pill cups were formed from the pellets
by injection molding at a temperature in the range of 320 to
480F. Test results as to the antibacterial activity of the
molded product was comparable to the results set forth with
regard to Example Io
Example XI
., .
~ xample X was repeated with the exception that
10.0%, by weight, of ortho-benzyl-para-chlorophenol was
incorporated and the antimicrobial loaded pellets dilluted
with sufficient non~loaded polypropylene pellets to arrive
at a concentration of 0.50% antimicrobial compound in the
molded articles.
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- Examp~e XII
Particulate film grade polyvinyl chlorlde was
admixed with 0.25%, by weight, of ortho-benzyl-para-chloro-
phenol in an extruder apparatus wherein the feedstock end of
the extruder barrel was maintained at a temperature in the
range of 275 to 325F and pellets formed. The pellets were
extruded in conventional apparatus, maintained at the extruder
head at about 480F, to form film ranging in thickness from
0.5 mils to 7.0 mils. Bacteriological tests indicated anti-
microbial activity comparable to that set~forth with regardto 3xample ~
Example XIII
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Pellets produced in accordance with Example II,
wherein brown and blue identifying colorant was added, which -
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pellets were molded at different times and stored under normal
storage conditions for two and three years respectively were
subjected to analysis to determine the antibacterial activity.
The tests showed the following:
' Samples Identified as: (1) "Brown" ~ellets
(2) "Blue" Pellets
Test Performed: Antibacterial Activity
Method Empl~yed: AATCC Test Method 90-1970
Antibacterial Activity of Fabrics,
Detection of: Agar Plate Method
Test Media: AATCC Agar and Blood Agar Plates
Te~t Organisms: Staphylococcu _aureus
. ,
Pseudomonas aeru~inosa
Escherichia coli
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Test Organism (Cont.): Streptococcus virldans (alpha
hemoLytic)
Incubation: 24 hours at 37C
16 hours at 4~C, then 8 hours at
37C
Zone of Inhibition in Millimeters
Organism Medium 37C 4C, then 37C
.
Brown Blue Brown Blue
S. aureus AATCC 5.0 5.0 7.0 7.0
BAP 4.0 2.0 3.0 2.Q
Ps. aeruginosa AATCC 0.0 0.0 0.0 0.0
BAP 7.0 3.0 2.0 0.0 -
E. coli AATCC 1.0 0.0 1.0 0.0 `~
BAP 0.0 0.0 2.0 0.0 ; :~
S. viridans AATCC No growth No growth
BAP 3.0 2.0 4.0 3.0
CONCLUSION:
. : .
The Brown Pellets and the Blue Pellets exhibited
antibacterial action against S. aureus, E. coli and S. viri-
dans grown on AA~CC Agar and antibacterial action against ~;
S. aureus, Ps. aeruginosa, E. coli and S. viridans grown on
Blood Agar when tested by the Standard Methods. The diffe-
rences in the diameters of the zones o~ inhibition may be
interpreted as indicative of the relative susceptibility of
the various organisms to the agent contained in the pellets.
The presence of a de~inite zone of inhibition of any size may
b- regarded as si~nificant.
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