Note: Descriptions are shown in the official language in which they were submitted.
W O 92/15198 21~ 4 ~ 6 2 PC~r/~S91/09116
ORAL & PERSONAL HYGIENE ARTICLES
CONTAINING ACTIVE AGENTS
BONDED TO THE SURFACE THEREOF
SUMMARY OF T~E I~ENTION
This invention relates to articles suitable for oral
and personal hygiene use and comprised of polymeric
material wherein the articles have bonded to the surface
thereof one or more chemically or biologically active
agent(s). Some examples of suitable articles include eye
glasses, contact lens, toothbrushes, tooth picks,
dentures, dental floss, razors, hair brushes and combs.
The polymeric material is selected from the group
15 consisting of polyamides, polystyrenes, styrene-
acrylonitrile copolymers, acrylonitrile-butadiene-styrene
copolymers, polyacrylates, polyesters and polypropylenes;
preferably nylon and cellulose acetate propionate. The
active agent preferably is a quaternary ammonium
20 compound, such as 3-(trimethoxysilyl)
propyldimethyloctadecyl ammonium chloride.
This invention also relates to a method for applying
a coating of chemically or biologically active agent(s)
to an oral or personal hygiene article comprised of
25 polymeric material by (a) directly permanently bonding
said active agent to the surface of said article, or (b)
tl) contacting said articles with an acid, alkaline
hydroxide or organic solvent and (2) subsequently
permanently bonding said active agent(s) to the surface
30 of sàid article.
The invention yields oral and personal hygiene
articles which have anti-bacterial and/or anti-microbial
coatings and/or coatings of active agents useful in
retarding or preventing plague, gingivitis,
3-periodontitis, tooth and gum pain and diseases and
infections of the skin, hair, scalp and eyes.
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W092/15198 PCT/US91/09116
BACKGROUND OF THE INVENTION AND INFORMATION DISCLOSUR'
Oral and personal hygiene articles, such as
toothbrushes and dental floss and the like, are
constantly being improved for more effective cleaning and
other benefits. Some of the benefits include the
delivery of active agents to the teeth and gums and
disinfectant properties of the oral hygiene articles.
8ecause toothbrushes, hair brushes and combs, in
particular, can be a haven for bacterial and/or microbial
growth, it would be especially beneficial to provide a
toothbrush or other oral and personal hygiene articles
which inhibit or prevent the growth of bacteria and/or
other microbes thereon. Thus, it is an object of this
invention to provide oral and personal hygiene articles
15 which have one or more active agents bonded to the
surface thereof. It is a further object of this
invention to provide oral and personal hygiene articles
which possess permanent or long-lasting anti-bacterial
and/or anti-microbial activity. It is another object of
20 this invention to provide an easy and efficient method
for applying a coating of active agent(s) to an oral or
personal hygiene article by (a) directly permanently
bonding the active agent(s) to the surface of the article
or (b) by contacting it with an acid, alkaline base or
25 organic solvent and subsequently permanently bonding the
active agent(s) to the surface of the article.
Many references in the art describe antibacterial
compositions and the use of these to treat various
surfaces. US Patent No. 4,866,192 describes
30 organosilicone quaternary ammonium antimicrobial
compounds to treat rayon fabric and other surfaces. US
Patent No. 4,371,577 describes antimicrobial carpet which
has been treated with an amino acid type surfactant and
an organosilicone quaternary ammonium salt. US Patent
35 No. 4,621,120 describes antibacterial compositions
comprising vinyl copolymers having quaternary nitrogen
groups. These compositions are disclosed as being useful
in mouthwashes, toothpastes and dental creams.
US Patent No. 3,170,90l describes quaternary
ammonium compounds and polymers thereof which are useful
in treating paper and textile fabrics for imparting
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WO92/15198 PCT~US91/09116
- increase wet strength, water repellency, and resistance
to shrinkage. US Patent No. 4,025,617 describes
antimicrobial quaternary--ammonium copolymers formed by
the condensation of at least two di-functional tertiary
amines and 1,4-dihalo-2-butene. These copolymers are
i described as being useful for the antimicrobial treatment
of circulatory and standing waters.
US Patent No. 4,482,680 discloses poly(vinylbenzyl
quaternary ammonium) halides which are useful as
preservatives for cosmetic and pharmaceutical
compositions and as disinfectant cleansers. US Patent
No. 4,161,518 describes dentifrice compositions
containing a quaternary ammonium organosilicone. US
Patent No. 4,394,378 describes certain silyl quaternary
ammonium salts, such as 3-(trimethoxylsilyl)
propyldidecylmethyl ammonium chloride, which is useful
for antimicrobial treatment of textile fibers, siliceous-
materials, rnetals, leather, wood and plastics.
US Patent No. 4,161,518 describes dentifrice
20 compositiOns containing a quaternary ammonium
organosiloxane which is useful in inhibiting plaque
formation on teeth. US Patent No. 4,615,937 describes
antimicrobially-active web and wet wipes containing an
organosilicone quaternary ammonium salt. US Patent No.
2~ 4,721,511 describes antimicrobial fabrics having a
bioactive amount of a silicone quaternary amine. US
Patent No. 4,282,366 describes natural and synthetic
fabrics impregnated with organosilicone quaternary
ammonium compounds as antimicrobial agents.
A method for preparing antimicrobial foams
containing guaternary ammonium salts of silanes is
described in US Patent No. 4,631,297. US Patent No.
4,408,996 describes a process for dying bioactive
cellulosic fabrics by applying a mixture of
3~ organosilicone polymer, a dye and a silyl quaternary
amine.
US Patent No. 3,730,701 describes a method for
controlling the growth of algae in water by adding
certain silyl quaternary amines. US Patent No. 4,847,088
describes synergistic antimicrobial compositions
comprising a quaternary ammonium compound and an acid
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WO92/15198 ~0 4 ~ 6 2 PCT/US91/09116
which are useful in treating carpets, fabrics, walls and
furnishings.
Articles, such as "Disinfection of Water with
Quaternary Ammonium Salts Insolubilized on a Porous Glass
Surface," Nakagawa et al, A~plied and Environmental
Microbioloay, March 1984, p-513-518; and "Algicidal
Activity of a Surface-Bonded Organosilicone Quaternary
Ammonium Chloride," Walters et al, AP~lied MicrobioloqY,
Feb. 1973, P. 253~256 describe the antimicrobial activity
~0 of bound quaternary ammonium salts.
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WO92/15198 PCT/US91/09]16
DETAILED DESCRI_TION
The present invention relates to personal and
oral hygiene products which have been treated to bond
active agent(s)to their surfaces. Specifically, the
present invention involves an article comprised of
polymeric material having bonded to the surface thereof
one or more chemically or biologically active agent(s),
wherein said article is suitable for oral or personal
hygiene use, and said active agent is substantially
l0 non-leachable from the surface of said article in a
water-based medium.
Articles covered by this invention include any
article of manufacture which is suitable for oral or
personal hygiene use. Oral hygiene as used herein means
useful for cleaning and caring for the teeth, gums,
dentures or any other parts of the oral cavity. Personal
hygiene as used herein means useful for cleaning and
caring for the hair, scalp, skin, ears, nose, eyes and
other parts of the face and head. Preferred articles
20 within the scope of this invention include a toothbrush,
dental floss, toothpick, comb, hair brush, razor,
eyeglass lens and frames and contact lens.
Suitable articles according to this invention may be
composed partly or entirely of a polymeric material or
2~ have an exterior surface comprised of a polymeric
material. The polymeric material can be a natural or
synthetic polymer. The polymeric material preferably is
polyamides, polyacrylates, polyesters, polypropylenes,
polystyrenes, styrene-acryl-onitrile copolymers,
acrylonitrile-butadien-
estyrene copolymers, cellulose esters and blends andcombinations thereof. The most preferred polymeric
materials are nylon and cellulose acetate propionate.
3- An essential feature of this invention is that the
article has permanently bonded to the polymeric surface
thereof one or more chemically or biologically active
agent(s). These active agent(s) are bonded to the
polymeric surfaces of the article, such that the agent(s)
are substantially non-leachable from the surface of said
article in a water-based medium. Suitable active agents
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W092/1~198 PCT/US91/091]6
would include any compound(s) having antimicrobial
activity and which are capable of being bonded to the
polymeric surfaces of the article. Preferred active
agents include the quaternary ammonium compounds,
; organosilicone quaternary ammonium compounds, cetyl
pyridinium compounds, guanidine compounds, bis-guanidine
compounds and isothiouronium halide compounds.
Preferred quaternary ammonium compounds useful for
this invention have the formula:
~ r 1 1 ~
R3 - N+ - R4-Y X
R2
Wherein Rl is CH2-phenyl or an alkyl group
containing about 8-22 carbon atoms; R2 is methyl, ethyl
or an alkyl group containing about 8-22 carbon atoms; R3
is methyl or ethyl; R4 is an alkyl group containing about
1-6 carbon atoms; X is an anion; and Y is a group having
the structure:
-Z, -OH, -OR5, -OC(O)R6, -CN,
O O O
D D
25O-S-OQ, -C-O-R7 -C_CH, -S-R8, -S-Rg,
O
-S-Rl -N-Rll ~ ANl;s -CH=CH2,
R12
5~ R6~ R7~ R5~ Rg, Rlo, Rll, R12, are alkyl
groups containing about 1-12 carbon atoms or phenyl; Z is
halogen and Q is hydrogen or a cation.
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W092/15198 2 1 ~ `~ 4 6 ~ PCT/US91/09116
The more preferred organosilicone quaternary
ammonium compounds useful for this invention have the
formula:
CH30)3 Si(CH2)n I R3 ~
wherein Rl, R2, and ~3 are as described above, X is an
anion and n is an integer from about 1-6 (preferably
3-6).
The most preferred organosilicone quaternary .;
15 ammonium compounds are
n-octadecyldimethyl[3-(trimethoxysilyl)propyl] ammonium
chloride, n-tetradecyldimethyl [3-(trimethoxysilyl)
propyl] ammonium chloride, n-decyldimethyl[3-(trimethoxy-
silyl)propyl] ammonium chloride,
n-didodecylmethyl[3-(tri-
methoxysilyl)propyll ammonium chloride, and n-dodecyldi-
2~ methyl¦3-(trimethoxysilyl)propyl] ammonium chloride. . :
Other active agents can include the nitrogen as part ~-
of a heterocyclic system, such as a cetyl pyridinium
compound. The preferred.cetyl pyridinium compound is
30 2-(3-trimethoxy-
æilylpropyl)-N-cetyl pyridinium bromide.
The isothiouronium halide compounds are also
suitable for use as active agents according to this
invention. The preferred isothiouronium halide compound
for u~e in this invention is (trimethoxysilylpropyl)
isothiouronium chloride.
The articles of this invention have the active
agent(s) bonded to the polymeric surfaces of the
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W092/15198 ~10 4 4 6 2 PCT/US91/09116
articles, such that the active agent(s) is permanently
attached to the articles. To be suitable for oral and
personal hygiene use, the articles must have the active
agent(s) bonded to the polymeric surfaces thereof such
that the agent(s) is substantially non-leachable in an
aqueous medium. Thus, the articles have a polymeric
surface which has permanent antibacterial and/or
antimicrobial activity which can not be leached out by
saliva, shampoos, shaving creams, toothpastes and other
aqueous-containing mediums.
The active agents can be permanently attached to the
polymeric surfaces of the articles by any suitable means,
~uch as chemical linking using multifunctional reactive -
organics (such as bis-carbenes or bis-nitrenes), silane
coupling systems, plasma activation, flame activation,
chemical treatment and other polymer grafting techniques.
The preferred attachment mechanism is a silane
coupling system. It is believed, although Applicant does
2~ not intend to be limited thereby, that the alkoxysilyl
end of the active agent is hydrolyzed to the
corresponding hydroxy component in the presence of water.
This component then reacts with the active -OH, amide or
30 other reactive sites on the polymeric material. Although
the active agent can be bonded to the polymeric surface
of the article by any type of bonding, it is preferred
that the agent be covalently bonded to the polymeric
surface of the article.
The present invention also includes a method for
applying a coating of chemically or biologically active
agent to an oral or personal hygiene article comprised of
polymeric material. This method can involve permanently
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W092~15198 ~ 4 6 2 PCT/US91/09116
bonding the active agent directly to the untreated
surface of the article. The method can also comprise the
steps of:
l. contacting said article with a solvent selected
from the group consisting of an aqueous-based
organic or inorganic acid, an aqueous-based
alkaline hydroxide or an organic solvent, and
2. subsequently bonding said active agent to the
surface of said article.
The invention also includes articles which have been
treated by the above ~ethods.
l~ It iQ believed, although Applicant does not intend
to be bound or limited hereby, that treating the
polymeric surface sf the article with the solvent exposes
or forms reactive sites on the polymeric surface to which
the active agents can bond. Preferably, the polymeric
surface of the article has greater than about 2% of the
surface area containing active sites for bonding of the
2~ active agent; more preferably greater than about 5%.
Thus, suitable solvents for treating the polymeric
surfaces of the article include any material which would
expose or form reactive -OH, amide, or other reactive
30 sites on the polymeric surfaces for bonding of the active
agents. Some examples of suitable solvents include
aqueous-based organic and inorganic acids, aqueous-based
alkaline hydroxides and organic solvents. The preferred
acids are sulfuric and acetic acid. The preferred
alkaline hydroxides are potassium hydroxide and sodium
hydroxide. Preferred organic solvents include methanol,
ethanol, isopropanol, acetone and ethyl acetate.
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WO 92/15198 ~ 4 ~ 2 PCI`/US91/09116
The polymeric surfaces of the articles are contacte~
with the solvent for a sufficient time ranging anywhere
from a few minutes to several hours. The solvents can be
u~ed alone, in combination or sequentially.
In bonding the active agent to the polymeric surface
of the article, the article can be contacted with the
active agent for a sufficient time for the active agent
10 to bond to the surface. Preferably, the active agent is
in a solution of water or other suitable solvent. The
solution can contain the active agent in any
concentration, but preferably contains from about 1% to
about 4% wt./vol. of the active agent. After contacting
the article with the solution of active agent for a
sufficient period of time (preferably about 30 minutes or
longer), the article can be dried, rinsed and c~red at an
elevated temperature (preferably about 50-125C). The
drying and curing conditions,such as temperature, time
and humidity, should be selected such that the
2S dimensional stability of the article is not adversely
affected.
The articles of this invention are effective against
a wide variety of microbial species, and they
30 continuously inhibit the growth of microbial organi~ms on
the surface thereof. The articles have demonstrated
antimicrobial activity against Candida albicans,
Pseudomonas aeruginosa, Staphylococcus aureus,
Escherichia coli, Streptococcus mutans/faecalis and
Klebsiella pneumoniae.
The following examples are presented to help
demonstrate the present invention. The examples are
intended to be illustrative and not in a limitative
,.
WO92/15198 ~ 4 4 6 ~
sense. This invention includes the embodiments described
and exemplified herein and all equivalents thereof. All
parts and percentages used in the examples are on a
weight basis unless otherwise indicated.
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WO92/15198 2 1 ~ 6 2 PCT/US91/09116
EXAMPLE I
Various treatment solutions were prepared within the
scope of this invention containing 1%, 2% and 4%
wt./vol., respectively, of the active agent. Each
solution was prepared by mixing lO ml. of concentrated
acetic acid and 2 grams of surfactant (Zonyl FSN from
DuPont Co.) with deionized water, followed by either lO,
20 or 40 grams of the active agent, to make one liter of
each solution. The solution is agitated for about 30
minute~ to hydrolyze the active agent.
These solutions are presented in Table I below:
~ .
TABLE I
Solution Active Aqent Amt. (Wt.~Vol.)
Sample l n-octadecyldimethyl 13-(trimethoxy-
silyl)propyl] ammonium chloride 1%
20 Sample 2 " 2%
Sample 3 " 4%
Sample 4 n-tetradecyldimethyl ]3-trimethoxy-
silyl)propyl] ammonium chloride 1%
2~ Sample 5 " 2%
Sample 6 " 4%
Sample 7(trimethoxysilylpropyl)
isothiouronium chloride 1%
Sample 8 " 2%
30 Sample 9 " 4%
Sample lO2-(3-trimethoxysilylpropyl)-N-cetyl
pyridinium bromide 1%
Sample ll " 2%
Sample 12 ~ 4%
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WO92/1519~ PCT/US91/09116
EXAMPLE II
Nylon toothbrush bristle fibers were treated with
the solutions of samples 1-3 by agitating the bristles in
the respective solutions for about 30 minutes. The
bristle fibers were removed from the solutions and dried
at ambient conditions for about 3 hours. The fibers were
then rinsed with deionized water and heated in an oven
for about lO minutes at about 125C. The fibers were
cooled at room temperature and the samples were place in
inocula of Staphylococcus aureus, Pseudomonas aeruginosa
and Candida albicans, respectively. The fibers were then
removed from the inocula. One sample from each inoculum
wa~ placed immediately in Letheen Broth, agitated, and a
sample of the broth was then plated onto plate count agar
via spiral plater. The numbers of colony forming units
per milliliter were measured. Other samples from each
inoculum were allowed to dry for l hour or 23 hours-
before being placed in the Letheen Broth as described
above. Bristle fibers not treated with the active agent
20 solutions were used as a control and evaluated in tandem
with the treated bristles. The results are presented in
Table II below.
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W O 92/15198 PCT~US91/09116
2~0~ 2
TA3LE II
-
Microorganism: Staphylococcus sureus
SAMPLEINITIAL* 1 HOUR* % CHANGE 23 HOUR* % CHANGE
CONTROL 2.7 X 1052.1 X 105-22.2 3.7 X 105 +37.0
..
SAMPLE 3 2.4 X 1052.2 X 10~ -8.3 7.1 X 103 -97.0
SAMPLE 2 1.8 X 1051.4 X 105-22.2 1.2 X 104 -93.3
. _
SAMPLE 1 3.3 X 1052.6 X 105-21.2 6.5 x 104 -80.3
Microorganism: Pseudomonas aeruginosa
S S
CONTROL 8.0 X 104.6 X 10 -42.5 1.9 X 103 -99.8
SAMPLE 3 5.5 X 103.1 X 10 -43.6 7.1 x lol -99 9
1~SAMPLE 2 3.6 X 1053.3 X 105 -8.3 5.4 X 10 -99.9
5 e
SAMPLE 1 4.9 X 104.7 X 10~ -4.1 1.85 X 10 -99.9
Microorganlsm: Candida albicans
- CONTROL 3.9 X 104 3.9 X 104 o 2.1 X 103 -94.6
SAMPLE 3 3.9 X 1044.1 X 104+5.1 9.8 x 10l -99.8
. _
SAMPL~ 2 5.9 X 1046.5 X 104+10.2 8.7 X 102 -98.5
SAMPLE 1 4.2 X 1043.2 X 104-23.8 3.1 X 103 -92.6
* (Colony forming units per ml.)
- 15 - 21~4~2
WO92/15198 PCT/US91/09116
EXAMPLE III
Following the procedures of Example II, toothbru-qh
headq comprisçd of cellulose acetate propionate were
treated with the solutions of Samples 1-3 and evaluated
for antimicrobial activity. The r~sults are presented in
Table III below.
TABLE III
Microorganism: Staphylococcus sure~s
SAMPLE INITIAL* 1 H0UR* % CHANGE 23 HOUR* % CHANGE
CONTROL 12.0 X 1061.6 X 106 -20.0 1.9 X 106-5.0
CONTROL 22.0 X 1061.6 X 106 -20.0 1.8 X 10-10.0
SAHPLE 32.0 X 10 5.7 X 105 -71.5 8.7 X 10-99.9
.
SAMPLE 22.0 X 1066.7 X 105 -66.5 1.5 X lo2_99 9
SAMPLE 12.0 X 1065.5 X 105 -72.5 2.0 x 1o2_99.9
Microorganlsm: Pseudomonas aeruginosa : . -
CONTROL 11.7 X 1061.2 X 106 -29.4 6.0 X 105-64.7
CONTR~L 21.7 X 1061.1 X 106 -35.3 3.8 x 105-77.7
SAMPLE 31.6 X 1061.2 X 106 -25.0 1.4 x 105-91.3
SAMPLE 21.7 X 1061.2 X 106 -29.4 5.0 X 104-97.1
- 6 5
2~ 5AMPLE 11.7 X 1061.2 X 10 -29.4 3.2 X 10-81.2
Microorganism: Candida albicans
4 5
C0NTROL 12.0 X 106.0 X 10 -70.0 7.8 X 10+290.0
CONTROL 21.9 X 1056.4 X 104 -66.3 4.3 x 105+126.3
30 SAMPLE 32.4 X 1055.1 X 104 -78.8 1.5 x 103-99.4
.
SA~PLE 2_1.6 X 1053.4 X 104 -78.8 1.6 X 101_99 9
SAMPLE 11.7 X 1055.5 X 104 -67.7 Z.4 X lo2_99 9
* (Colony forming units per ml.)
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WO92/15198 21~62 16 - PCT/US91/09]16
EX~MPLE IV
Following the procedures of Example II, toothbrush
headR compri~ed of cellulose acetate propionate were
treated with the solutions of samples 4-6 and evaluated
for antimicrobial activity. The results are present in
Table IV below.
TABLE IV
Microorganism: Staphylococcus aureas
SAMPLE INITIAL* 1 HOUR* % CHANGE 23 HOUR* % CHANGE
CONIROL 5.1 X 105 7.5 X 105 +47.1 4.9 X 105-3.9
. _
SAMPLE 6 4.2 X 105 8.8 X 104 -79.1 1.5 X lo2-99 9
_
~3 SAHPLE 5 5.4 X 10 3.~ X 105 -35.2 1.8 X 105-66.7
-
SAMPLE 4 3.3 X 105 2.9 X 105 -12.1 1.1 x 103-99.7
Microorganism: Pseudomonas Aeruginosa
CONTROL 7.9 X 105 5.9 X 105 -25.3 1 8 X 102-99 9
---
SAHPLE 6 7.5 X 105 6.1 X 105 -18.7 6.4 x lo2-99 9
SAMPLE 5 7.9 X 105 6.9 X 105 -12.7 1.8 X 103-99.8
.
SAMPLE 4 8.0 X 105 6.6 X 105 -17.5 1.6 X 102_99.9
Microorgan$sm: Candlda albicans
3 3 2
CONTROL 5.5 X 10 5.5 X 10 01.1 X 10 -98.0
SAMPLE 6 1.1 X 10 6.7 X 103 -39.1 0 -100.0
. _ . _ . _
SAMPLE 5 1.5 X 10 9.5 X 103 -36.7 7.1 X 101 -99.5
30 ~AMPLE 4 8.5 X 103 5.7 X 103 -32.9 0 -100.0
* (Colony forming units per ml.)
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W O 92/15198 ` PCT/US91/09116
E~MPLE V
Following the procedures of Example II, toothbrush
heads comprised of cellulose acetate propionate were
treated with the ~olutions of Samples 7-9 and evaluated
for antimicrobial activity. The results are presented in
Table V below.
TABLE V
~0 Microorganism: Stsphylococcus aureas
SAMPLE INITIAL* 1 HOUR*% CHANGE 23 HOUR* % CHANGE
CONTROL 5.7 X 105 4.9 X 105 -13.6 1.2 X 106 +102.4
:
SAMPLE 9 5.7 X 105 4.0 X 10-93.0 5.2 X 103-99.1
1~ SAMPLE 8 6.6 X 105 1.8 X 104 -97.3 1.9 X 104 -97.1
SAMPLE 7 6.9 X 105 4.8 X 105 -99.3 9.8 x 105 +41.0
.
Microorganlsm: Pseudomonas aeruginosa
CONTROL 2.1 X 106 2.2 X 106 +5.3 2.3 X 105 -88.7
SAMPLE 9 2.2 X 106 2.1 X 10-3.2 4.4 x lol-99 9
SAMPLE 8 2.2 X 106 2.1 X 106 -5.5 7.3 X 104 -96.6
SAMPLE 7 2.2 X 106 2.2 X 106 0 3.8 X 103 -99.8
_
2~ Microorganism: Candida albicans
CONTROL 1.4 X 10 6.4 X 10-54.5 2.1 X 10-85.1
SAMPLE 9 6.3 X 10 4.6 X 102 -92.7 1.1 X 101 -99.8
SAMPLE 8 1.5 X 104 2.0 X 103 -86.5 1.1 X 103 -92.7
30 SAMPLE 7 2.4 X 104 7.1 X 104 +195.43.3 X 104 +37.9
. . .
* tColonY forming units per ml.) f -
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WO92/15198 2 1 0 ~ ' ~ '' PCT/US91/09116
_ ~ J h EXAMPLE VI
Following the procedur~s of Example III, toothbrush
heads compri~ed of cellulose acetate propionate were
treated with the solutions of Samples 10-12 and evaluated
for antimicrobial activity. The results are pre~ented in
Table VI below.
TAB~ VI
Microorganism: Staphylococcus aureas
10 SAHpLE INITIAL* 1 HOUR* % CHANGE 23 HOUR* % CHANGE
CONTROL 2.9 X 105 2.0 X 105 -31.02.2 X 105 -24.1
.
SAMPLE 12 2.7 X 105 1.4 X 105 -48.11.7 X 104 -93.7
.
SAMPLE 11 3.1 X 105 2.1 X 105 -32.32.0 X 104 -93.6
''SAMPLE 10 3.2 X 105 2.4 X 105 -25.04.8 x 104 -85.0
Microorganism: Pseudomonas aeruginosa
. .
CONTROL 6.7 X 105 6.4 X 105 -4.5 2.7 X 103 -99.6
SAMPLE 12 6.8 X 105 6.9 X 105 +1.5 3.9 x lo2 -99 9
SAHPLE 11 6.0 X 105 4.5 X 105 -25.0 7.1 X 103 -99.9
SAMPLE 10 8.7 X 105 6.7 X 105 -23.0 2.1 X 103 -99.8
. _
Microorganism: Candida albicans
2~CONTROL 3.5 X 10 3.1 X 10 -11.41.4 X 10 -99.6
.
SAMPLE 12 4.4 X 10~ 2.5 X 104 -43.22.9 X lo2 -99 3
SAMPLE 11 3.3 X 104 3.2 X 104 -3.0 6.0 X 102 -98.2
SAHPLE 10 4.0 X 104 3.4 X 104 -15.09.7 X 102 -99.6
30 - _
* (Colony forming units per ml.)
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W092/lS198 PCT/US91/Ogll6
EXAMPLE VII
Toothbrush heads comprised of cellulose acetate
propionate,and treated with the solution of Sample 3
according to the procedures of Example II, were evaluated
for leachability of the active agent. Some of these
treated toothbrush heads were washed several times with
water, while others were unwashed.
The washed and unwashed toothbrush heads were
evaluated for leachability using a bromophenol blue
10 colorimetric analytical method. A bromophenol blue
solution was prepared by mixing 0.1125 grams bromophenol
blue, 450 grams of deionized water and 0.75 ml. of 10%
Na2C03. Two of the washed toothbrush heads were placed
in a 4-ounce french square bottle along with 50 ml. of
the bromophenol blue solution and 2 ml. of 2% Triton
X-100 wetting agent. Two of the unwashed toothbrush
heads were also placed in a similar bottle with 50 ml. of
the bromophenol blue solution and Triton wetting agent.
The bottles were shaken for about 20 minutes and allowed
to sit. After periods of 1-hour, 12-hours and 24-hours,
solution from each bottle was poured into cuvets and the
transmittance measured on a spectrophotometer at 589
nanometers.
In the procedure, the blue dye reacts with the bound
2~ active agent on the toothbrush heads, causing a decrease
in the bromophenol blue solution's color intensity. This
loss of color intensity is a quantitative measure of the
amount of active agent bonded to the surface of the
toothbrush heads.
~0 The results of the evaluation are presented in Table
VII below.
(Absorbance Units)
Sampling Time in Hours
SamDle (0) (1) (12) (24)
A. Washed Toothbrush Heads 0.32 0.30 0.31 0.33
B. Unwashed Toothbrush Heads 0.31 0.30 0.33 0.33
C. Bromophenol Blue Solution 0.53 0.53 0.53 0.53
Control
(sample to sample variation is less than ~ 0.02
absorbance units)
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WO92/15198 2 1 0 ~ ~ 6 2 - 20 - PCT/US91/09116
The above results show no significant differenc
between the washed and unwashed toothbrush heads,
indicating no leaching of the active agent initially or
over time.
i
SUBSTITUTE SHEET
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