U.S. patent application number 17/245331 was filed with the patent office on 2021-08-26 for anti-microbial polymer incorporating a quaternary ammonium group.
The applicant listed for this patent is CHEMGREEN INNOVATION INC.. Invention is credited to Felix Baerlocher, Khashayar Ghandi, Zahid Shabbir Mahimwalla.
Application Number | 20210259243 17/245331 |
Document ID | / |
Family ID | 1000005582802 |
Filed Date | 2021-08-26 |
United States Patent
Application |
20210259243 |
Kind Code |
A1 |
Ghandi; Khashayar ; et
al. |
August 26, 2021 |
ANTI-MICROBIAL POLYMER INCORPORATING A QUATERNARY AMMONIUM
GROUP
Abstract
The present disclosure relates to anti-microbial polymers
comprising a polymerizable cyclic moiety which forms part of the
backbone of the polymer.
Inventors: |
Ghandi; Khashayar;
(Sackville, CA) ; Mahimwalla; Zahid Shabbir;
(Sackville, CA) ; Baerlocher; Felix; (Sackville,
CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
CHEMGREEN INNOVATION INC. |
Sackville |
|
CA |
|
|
Family ID: |
1000005582802 |
Appl. No.: |
17/245331 |
Filed: |
April 30, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14418549 |
Jan 30, 2015 |
10993437 |
|
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PCT/CA2014/000505 |
Jun 18, 2014 |
|
|
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17245331 |
|
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61836360 |
Jun 18, 2013 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61L 2300/208 20130101;
A61K 8/0208 20130101; C08F 32/02 20130101; C08G 73/026 20130101;
A61L 31/16 20130101; A01N 43/90 20130101; A61L 29/085 20130101;
A61L 2300/404 20130101; A01N 43/38 20130101; A01N 33/12 20130101;
A61L 29/16 20130101; B65D 65/42 20130101; A61L 31/10 20130101; A01N
43/50 20130101; A01N 43/48 20130101; C08F 232/00 20130101; A61K
8/817 20130101; D21H 17/45 20130101; A61L 27/34 20130101; C08F
32/00 20130101; A01N 43/46 20130101; A01N 43/40 20130101; D21H
21/36 20130101; A01N 43/42 20130101; C08G 73/0627 20130101; B65D
81/24 20130101; A61Q 19/10 20130101; A61L 27/54 20130101; A61Q
17/005 20130101; A01N 37/44 20130101 |
International
Class: |
A01N 33/12 20060101
A01N033/12; A61L 31/10 20060101 A61L031/10; A01N 43/90 20060101
A01N043/90; A61L 27/34 20060101 A61L027/34; A61Q 17/00 20060101
A61Q017/00; A61K 8/81 20060101 A61K008/81; D21H 21/36 20060101
D21H021/36; A61L 31/16 20060101 A61L031/16; A61L 29/16 20060101
A61L029/16; D21H 17/45 20060101 D21H017/45; A61Q 19/10 20060101
A61Q019/10; A61K 8/02 20060101 A61K008/02; A61L 27/54 20060101
A61L027/54; A61L 29/08 20060101 A61L029/08; C08F 232/00 20060101
C08F232/00; C08F 32/02 20060101 C08F032/02; C08F 32/00 20060101
C08F032/00; A01N 37/44 20060101 A01N037/44; A01N 43/40 20060101
A01N043/40; B65D 65/42 20060101 B65D065/42; B65D 81/24 20060101
B65D081/24; C08G 73/02 20060101 C08G073/02; C08G 73/06 20060101
C08G073/06 |
Claims
1. An anti-microbial polymer, comprising polymerizable units of i)
at least one monomer comprising a polymerizable aromatic moiety
containing an aromatic group, wherein the aromatic group is
covalently incorporated into the polymer backbone through loss of
aromaticity, and wherein the aromatic group comprises a quaternary
aromatic ammonium or phosphonium salt, a quaternary aromatic
ammonium or phosphonium salt, or quinone or quinone derivative; and
wherein the monomer further comprises an anti-microbial moiety,
wherein the anti-microbial moiety is a quaternary ammonium moiety
or a quaternary phosphonium moiety.
2. The anti-microbial polymer of claim 1, further comprising
polymerizable units of at least one unsaturated monomer having an
ethylenically unsaturated double or triple bond.
3. The anti-microbial polymer of claim 1, wherein the quaternary
aromatic ammonium salt comprises a monomer of the formula
##STR00031## wherein Ar is optionally substituted
(C.sub.6-C.sub.14)-aryl or optionally substituted
(C.sub.5-C.sub.14)-heteroaryl, Y is absent,
(C.sub.1-C.sub.10)-alkylene, (C.sub.2-C.sub.10)-alkenylene, or
(C.sub.2-C.sub.10)-alkynylene, wherein 1 or 2 carbon atoms are
optionally replaced with N, S or O; R.sub.1, R.sub.2 and R.sub.3
are independently or simultaneously optionally substituted H,
(C.sub.1-C.sub.24)-alkyl, (C.sub.2-C.sub.24)-alkenyl,
(C.sub.2-C.sub.24)-alkynyl, (C.sub.6-C.sub.14)-aryl,
(C.sub.5-C.sub.14)-heteroaryl or
(C.sub.1-C.sub.10)-alkylene-(C.sub.6-C.sub.14)-aryl, wherein the
optional substituents are chosen from one or more of halogen,
hydroxyl, (C.sub.1-C.sub.6)-alkoxy, thionyl, nitro, amino
(--NH.sub.2), (C.sub.6-C.sub.14)-aryl or
(C.sub.5-C.sub.14)-heteroaryl, and X is any suitable
counteranion.
4. The anti-microbial polymer of claim 3, wherein Ar is optionally
substituted phenyl, naphthyl, anthracenyl, 1,2-dihydronaphthyl,
1,2,3,4-tetrahydronaphthyl, fluorenyl, indanyl, indenyl, thienyl,
furyl, pyrrolyl, pyrididyl, indolyl, quinolyl, isoquinolyl,
tetrahydroquinolyl, benzofuryl, or benzothienyl.
5. The anti-microbial polymer of claim 4, wherein Ar is optionally
substituted phenyl.
6. The anti-microbial polymer of claim 3, wherein Y is
(C.sub.1-C.sub.6)-alkylene, (C.sub.2-C.sub.6)-alkenylene, or
(C.sub.2-C.sub.6)-alkynylene, wherein 1 or 2 carbon atoms are
optionally replaced with O.
7. The anti-microbial polymer of claim 3, wherein R.sub.1, R.sub.2
and R.sub.3 are independently or simultaneously
(C.sub.1-C.sub.24)-alkyl, (C.sub.2-C.sub.24)-alkenyl,
(C.sub.2-C.sub.24)-alkynyl, or
(C.sub.1-C.sub.10)-alkylene-(C.sub.6-C.sub.14)-aryl.
8. The anti-microbial polymer of claim 3, wherein the quaternary
aromatic ammonium salt comprises a monomer of the formula
##STR00032## wherein Y' is (C.sub.1-C.sub.3)-alkylene, wherein 1
carbon atom is optionally replaced with O; R.sub.1' and R.sub.2'
are independently or simultaneously (C.sub.1-C.sub.4)-alkyl
optionally substituted with --OH; R.sub.3' is
(C.sub.1-C.sub.24)-alkyl or
(C.sub.1-C.sub.10)-alkylene-(C.sub.6-C.sub.14)-aryl, and R is one
or more optional substituents chosen from halogen,
(C.sub.1-C.sub.6)-alkyl, thionyl, nitro, (C.sub.6-C.sub.14)-aryl or
(C.sub.5-C.sub.14)-heteroaryl, and X is halo.
9. The anti-microbial polymer of claim 8, wherein the quaternary
aromatic ammonium salt comprises ##STR00033##
10. The anti-microbial polymer of claim 1, wherein the quaternary
aromatic ammonium salt comprises a monomer of the formula
##STR00034## wherein Ring B is an optionally substituted aromatic
moiety containing from 5 to 18 carbon atoms, in which from 0 to 4
carbon atoms are replaced with a heteroatom selected from N, O and
S, R.sub.4 is H, (C.sub.1-C.sub.24)-alkyl,
(C.sub.2-C.sub.24)-alkenyl, (C.sub.2-C.sub.24)-alkynyl,
(C.sub.6-C.sub.14)-aryl or (C.sub.5-C.sub.14)-heteroaryl, wherein
the optional substituents are chosen from one or more of halogen,
--OH, (C.sub.1-C.sub.6)-alkoxy, thionyl, nitro, amino (--NH.sub.2),
(C.sub.6-C.sub.14)-aryl, (C.sub.6-C.sub.14)-heteroaryl, or two
adjacent substituents are joined to form a methylene dioxy moiety,
and X is any suitable counteranion.
11. The anti-microbial polymer of claim 10, wherein Ring B is an
optionally substituted aromatic moiety containing from 5 to 14
carbon atoms, in which from 0 to 2 carbon atoms are replaced with a
heteroatom selected from N, O and S.
12. The anti-microbial polymer of claim 11, wherein the monomer is
##STR00035## wherein R.sub.4 is H, (C.sub.1-C.sub.24)-alkyl,
(C.sub.2-C.sub.24)-alkenyl, (C.sub.2-C.sub.24)-alkynyl,
(C.sub.6-C.sub.14)-aryl or (C.sub.5-C.sub.14)-heteroaryl, R is one
or more optional substituents chosen from halogen, --OH,
(C.sub.1-C.sub.6)-alkyl, (C.sub.1-C.sub.6)-alkoxy, thionyl, nitro,
amino (--NH.sub.2), (C.sub.6-C.sub.14)-aryl,
(C.sub.5-C.sub.14)-heteroaryl, or two adjacent substituents are
joined to form a methylene dioxy moiety, and X is any suitable
counteranion.
13. The anti-microbial polymer of 12, wherein the monomer is
##STR00036## wherein R.sub.4 is H or (C.sub.1-C.sub.24)-alkyl, and
X is any suitable counteranion.
14. The anti-microbial polymer of claim 1, wherein the quinone or
quinone derivative is a monomer of the formula ##STR00037## R is
one or more optional substituents chosen from halogen, OH,
(C.sub.1-C.sub.6)-alkyl, (C.sub.1-C.sub.6)-alkenyl,
(C.sub.1-C.sub.6)-alkoxy, thionyl, nitro, (C.sub.6-C.sub.14)-aryl,
(C.sub.5-C.sub.14)-heteroaryl, or two or more adjacent substituents
are joined together to form an optionally substituted aromatic or
non-aromatic monocyclic or polycyclic ring.
15. The anti-microbial polymer of claim 14, wherein the quinone or
quinone derivative is a monomer of the formula ##STR00038##
16. The anti-microbial polymer of claim 1, wherein the at least one
monomer having an ethylenically unsaturated double or triple bond
comprises acrylic acid, acrylates, styrene, a vinylpyridine,
2-butyne-1,4-diol, cis-2-butene-1,4-diol, vinyl acetate,
pentaerythritol allyl ether, linalool or acrylated epoxidized
soybean oil.
17. The anti-microbial polymer of claim 16, wherein the monomer
comprises ##STR00039## wherein M.sup.+ is any suitable
counter-cation.
18. The anti-microbial polymer of, wherein the polymer comprises
##STR00040## wherein R.sub.1, R.sub.2 and R.sub.3 are as defined in
claim 3; X is any suitable counteranion, and m, n and p are
independently or simultaneously integers between 1 and
1,000,000.
19. The anti-microbial polymer of claim 1, wherein the polymer
comprises ##STR00041## wherein R.sub.1, R.sub.2 and R.sub.3 are as
defined in claim 3, X is any suitable counteranion, and m, n and p
are independently or simultaneously integers between 1 and
1,000,000.
20. The anti-microbial polymer of any one of claims 1 to 28,
wherein the polymer is conjugated to cellulose or a cellulose
derivative.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a divisional application of U.S.
patent application Ser. No. 14/418,549 filed on Jan. 30, 2015,
which claims priority from PCT/CA2014/000505 filed on Jun. 18, 2014
which claims the benefit of priority from U.S. provisional
application No. 61/836,360 filed on Jun. 18, 2013, the contents of
which are incorporated herein by reference in their entirety.
FIELD
[0002] The present disclosure relates to anti-microbial polymers
and polymer composites comprising a polymerizable cyclic moiety
which forms part of the backbone of the polymer.
INTRODUCTION
[0003] Antimicrobial compounds and materials are chemicals capable
of reducing or inhibiting the growth and development of microbial
organisms such as fungi and bacteria. Such compounds play an
important role in a variety of applications and fields including
human health, by helping the prevention and treatment of
microorganism linked diseases, fish and animal farming, preventing
the decomposition of materials e.g. polyurethanes, wood and other
construction materials, preservation of food from spoilage by
various micro-organisms, disinfecting surfaces to prevent the
transmission of various infectious microorganisms etc.
[0004] Current technology generally relies on incorporating
anti-microbial compounds into materials with a delayed release
mechanism, or by incorporating the compounds into polymeric
materials at the processing (i.e. extrusion molding etc.) or
post-processing stage such as coatings. In both instances the
antimicrobial compounds leach out over time, depleting the
effectiveness of the material, and in the case of toxic biocides
can lead to adverse outcomes for human health, the environment or
the intended application and material performance.
SUMMARY
[0005] The present disclosure relates to novel anti-microbial
polymers. In particular, the disclosure relates to anti-microbial
polymers and polymer composites composed of repeating and
polymerizable units of [0006] i) at least one monomer comprising a
polymerizable cyclic moiety wherein the cyclic moiety forms part of
the polymer backbone, and wherein the monomer further comprises an
anti-microbial moiety.
[0007] In one embodiment, the at least one monomer comprising a
polymerizable cyclic moiety comprises an anti-microbial moiety,
which results in the anti-microbial polymer having anti-microbial
activity. In one embodiment, the anti-microbial moiety comprises a
quaternary aromatic ammonium salt, a quaternary cyclic aromatic
ammonium salt, or quinone or quinone derivative.
[0008] In another embodiment, the disclosure relates to
anti-microbial polymers and polymer composites composed of
repeating and polymerizable units of [0009] i) at least one monomer
comprising a polymerizable cyclic moiety wherein the cyclic moiety
forms part of the polymer backbone, and wherein the monomer further
comprises an anti-microbial moiety; and [0010] ii) at least one
unsaturated monomer having an ethylenically unsaturated double or
triple bond.
[0011] Also included in the present disclosure are anti-microbial
devices such as stents, in which the devices have been coated with
the anti-microbial polymer of the present disclosure.
[0012] Also included in the present disclosure are medical devices
which are composed of anti-microbial polymers of the present
disclosure, for example a stent composed of an anti-microbial
polymer of the disclosure.
[0013] Other features and advantages of the present application
will become apparent from the following detailed description. It
should be understood, however, that the detailed description and
the specific examples while indicating preferred embodiments of the
application are given by way of illustration only, since various
changes and modifications within the spirit and scope of the
application will become apparent to those skilled in the art from
this detailed description.
DRAWINGS
[0014] The disclosure will now be described in greater detail with
reference to the following drawings in which:
[0015] FIG. 1 is an NMR spectrum of a PAA-BZ polymer product in an
embodiment of the disclosure;
[0016] FIG. 2 is an FTIR spectrum of a PAA-BZ polymer product in an
embodiment of the disclosure;
[0017] FIG. 3 is an UV-Vis spectrum of a PAA-BZ polymer product in
an embodiment of the disclosure;
[0018] FIG. 4 is an FTIR spectrum of a PAA-BZ-CELL polymer product
in an embodiment of the disclosure;
[0019] FIG. 5 is an X-ray Diffraction (XRD) spectrum of a
PAA-BZ-CELL polymer, along with the reference peaks by the Joint
Committee on Powder Diffraction Standards (JCPDS) in an embodiment
of the disclosure;
[0020] FIG. 6 is an FTIR spectrum of a NAPPA-BZ polymer product in
an embodiment of the disclosure;
[0021] FIG. 7 is an UV-Vis spectrum of a NAPAA-BZ polymer product
dissolved in Dimethylformamide (DMF) in an embodiment of the
disclosure;
[0022] FIG. 8 is an FTIR spectrum of a PVP-BZ (High) polymer
product in an embodiment of the disclosure;
[0023] FIG. 9 is an NMR spectrum of a PVP-BZ (low) polymer product
in an embodiment of the disclosure;
[0024] FIG. 10 is an FTIR spectrum of a PVP-BZ (low) polymer
product in an embodiment of the disclosure;
[0025] FIG. 11 is an UV-Vis spectrum of a PVP-BZ (low) polymer
product in an embodiment of the disclosure;
[0026] FIG. 12 is an FTIR spectrum of a PVP-BZ (Med) polymer
product in an embodiment of the disclosure;
[0027] FIG. 13 is an UV-Vis spectrum of a PVP-BZ (Med) polymer
product in an embodiment of the disclosure;
[0028] FIG. 14 is an NMR spectrum of a PAA-PVP-BZ polymer product
in an embodiment of the disclosure;
[0029] FIG. 15 is a thermogravimetric analysis (TGA) of a PAA-BZ
polymer in an embodiment of the disclosure;
[0030] FIG. 16 is a differential scanning calorimetry (DSC) results
of a PAA-BZ polymer in an embodiment of the disclosure;
[0031] FIG. 17 is a differential scanning calorimetry (DSC) results
of a PAA-BZ crystals in H.sub.2O in an embodiment of the
disclosure;
[0032] FIG. 18 is an avoided level crossing signal for free radical
formed from addition of Mu to Bz at room temperature in an
embodiment of the disclosure;
[0033] FIG. 19 is an avoided level crossing signal for free radical
formed from addition of Mu to Bz at 30.degree. C. in an embodiment
of the disclosure;
[0034] FIG. 20 is a high field avoided level crossing signal for
free radical formed from addition of Mu to Bz at 30.degree. C. in
an embodiment of the disclosure;
[0035] FIG. 21 is a TF-AR Fourier power at 3.8 kG for free radical
formed from addition of Mu to Bz at 95.degree. C. in an embodiment
of the disclosure;
[0036] FIG. 22 is an Fourier transform of TF-AR of Bz with added
other monomer at low concentrations (less than 1M) at 35.degree.
C., 2.6 kG in an embodiment of the disclosure;
[0037] FIG. 23 are polarized optical micrographs (.times.100
magnification) of a 0.25 mole fraction solution of styrene in Bz in
the presence of initiator (AIBN) at 35.+-.5 C in an embodiment of
the disclosure;
[0038] FIG. 24 is an FTIR spectrum of the BZ homopolymer polymer
product in an embodiment of the disclosure;
[0039] FIG. 25 is an .sup.1H NMR spectrum of the BZ Homopolymer
product in an embodiment of the disclosure;
[0040] FIG. 26 is a .sup.13C NMR spectrum of the BZ Homopolymer
product in an embodiment of the disclosure;
[0041] FIG. 27 is an FTIR spectrum of the 2-Butyne-1,4-diol and
benzyldimethyltetradecylammonium chloride polymer product in an
embodiment of the disclosure;
[0042] FIG. 28 is an FTIR spectrum of the cis-2-Butene-1,4-diol and
benzyldimethyltetradecylammonium chloride polymer product in an
embodiment of the disclosure;
[0043] FIG. 29 is an FTIR spectrum of the styrene and
benzyldimethyltetradecylammonium chloride polymer product in an
embodiment of the disclosure;
[0044] FIG. 30 is an FTIR spectrum of the vinyl acetate and
benzyldimethyltetradecylammonium chloride polymer product in an
embodiment of the disclosure;
[0045] FIG. 31 is an .sup.1H NMR spectrum of the vinyl acetate and
benzyldimethyltetradecylammonium chloride polymer product in an
embodiment of the disclosure;
[0046] FIG. 32 is a .sup.13C NMR spectrum of the vinyl acetate and
benzyldimethyltetradecylammonium chloride polymer product in an
embodiment of the disclosure;
[0047] FIG. 33 is an FTIR spectrum of the styrene, acrylic acid and
benzyldimethyltetradecylammonium chloride polymer product in an
embodiment of the disclosure;
[0048] FIG. 34 is an FTIR spectrum of the vinyl acetate, acrylic
acid and benzyldimethyltetradecylammonium chloride polymer product
in an embodiment of the disclosure;
[0049] FIG. 35 is a .sup.1H NMR spectrum of the vinyl acetate,
acrylic acid benzyldimethyltetradecylammonium chloride polymer
product in an embodiment of the disclosure;
[0050] FIG. 36 is a .sup.13C NMR spectrum of the vinyl acetate,
acrylic acid benzyldimethyltetradecylammonium chloride polymer
product in an embodiment of the disclosure;
[0051] FIG. 37 is an FTIR spectrum of the pentaerythritol allyl
ether, acrylic acid and benzyldimethyltetradecylammonium chloride
polymer product in an embodiment of the disclosure;
[0052] FIG. 38 is an FTIR spectrum of the linalool, acrylic acid
and benzyldimethyltetradecylammonium chloride polymer product in an
embodiment of the disclosure;
[0053] FIG. 39 is a .sup.1H NMR spectrum of the linalool, acrylic
acid and benzyldimethyltetradecylammonium chloride polymer product
in an embodiment of the disclosure;
[0054] FIG. 40 is a .sup.13C NMR spectrum of the linalool, acrylic
acid and benzyldimethyltetradecylammonium chloride polymer product
in an embodiment of the disclosure;
[0055] FIG. 41 is an FTIR spectrum of the epoxidized acrylated
soybean oil, linalool and benzyldimethyltetradecylammonium chloride
polymer product in an embodiment of the disclosure;
[0056] FIG. 42 is an .sup.1H NMR spectrum of the linalool,
epoxidized acrylated soybean oil and
benzyldimethyltetradecylammonium chloride polymer product in an
embodiment of the disclosure;
[0057] FIG. 43 is a .sup.13C NMR spectrum of the linalool,
epoxidized acrylated soybean oil and
benzyldimethyltetradecylammonium chloride polymer product in an
embodiment of the disclosure;
[0058] FIG. 44 is an FTIR spectrum of the Linalool and
benzyldimethyltetradecylammonium chloride polymer product in an
embodiment of the disclosure;
[0059] FIG. 45 is a .sup.1H NMR spectrum of the linalool and
benzyldimethyltetradecylammonium chloride polymer product in an
embodiment of the disclosure; and
[0060] FIG. 46 is a .sup.13C NMR spectrum of the linalool and
benzyldimethyltetradecylammonium chloride polymer product in an
embodiment of the disclosure.
DESCRIPTION OF VARIOUS EMBODIMENTS
(I) Definitions
[0061] The term "anti-microbial polymer" as used herein refers to
polymers of the present disclosure which kill, inhibit, and/or
reduce microbial growth, for example, by inhibiting the
proliferation or viability of a microbe which is undesirable and/or
which disrupts a microbial cell. Microbes includes bacteria,
viruses, fungi, protozoa and the like.
[0062] The term "polymerizable cyclic moiety" as used herein refers
to an unsaturated moiety of a monomer which can participate in a
polymerization reaction. The unsaturated group or moiety may be an
aromatic or non-aromatic moiety which can participate in a
polymerization reaction. The unsaturated moiety, for example, a
benzene ring, directly participates in the polymerization reaction
to form part of the backbone of the polymer that is prepared from
the reaction.
[0063] The term "polymer backbone" as used herein refers to the
covalently bonded chain of repeating monomer units that form the
polymer. As would be understood, the polymer backbone may be
covalently attached to terminal functional groups or pendant
functionalized side chains spaced along the polymer backbone.
[0064] The term "anti-microbial moiety" as used herein refers to a
moiety, within the monomer comprising the polymerizable cyclic
moiety, that possesses anti-microbial activity and which can
therefore reduce kill, inhibit and/or reduce microbial growth. The
anti-microbial activity of the prepared anti-microbial polymer
exhibit similar or greater anti-microbial properties compared to
the individual monomers which form the polymer. The term
"anti-microbial moiety" also includes monomers which possess little
or no anti-microbial activity, but exhibit anti-microbial
properties upon polymerization to form the anti-microbial
polymer.
[0065] The term "ethylenically unsaturated" as used herein refers
to monomers having terminal, internal or pendant ethylenic
unsaturation or any combination thereof and which can participate
in a polymerization reaction. The ethylenic unsaturation may be a
double or triple carbon-carbon bond.
[0066] The term "aromatic" as used herein with respect to the
polymerizable cyclic moiety refers to a planar, cyclic or
polycyclic, ring moiety having a delocalized .pi.-electron system
containing 4n+2 .pi. electrons, where n is an integer. Aromatic
rings can be formed by five, six, seven, eight, nine, or more than
nine atoms. Aromatics can be optionally substituted and can be
monocyclic or fused-ring polycyclic. The term aromatic encompasses
both all carbon containing rings (e.g., phenyl) and those rings
containing one or more heteroatoms (e.g., pyridine).
[0067] The term "conjugated" as used herein with respect to the
polymerizable cyclic moiety refers to a moiety having two or more
double and/or triple bonds, each double or triple bond being
separated from the next consecutive double or triple bond by a
single bond so that .pi. orbitals overlap not only across the
double or triple bond, but also across adjacent single bonds
located between adjacent double and/or triple bonds. The double or
triple bonds may be carbon-carbon bonds or carbon-heteratom bonds,
such as carbonyl or imine moieties.
[0068] The term "quarternary ammonium moiety" or "quarternary
phosphonium moiety" as used herein refers to a moiety having four
bonds to the nitrogen or phosphorous atom with a positive charge on
the nitrogen or phosphorous in the "onium" state, i.e.,
"R.sub.4N.sup.+ or "quaternary nitrogen," wherein R is an organic
substituent such as alkyl or aryl. The term "quaternary ammonium
salt" or "quaternary phosphonium salt" as used herein refers to the
association of the quaternary ammonium or phosphonium with a
cation.
[0069] The term "quinone" as used herein refers to mono- and
poly-nuclear quinones such as benzoquinone, naphthoquinones,
anthraquinones, phenanthraquinone, camphor-quinone and addition
products and substituted derivatives thereof. The term "quinone"
also includes isomers of such quinones. The quinones may contain
substitution groups such as halogens, amino, alkyl, aryl, alkaryl,
aralkyl, alkoxy, aroxyl, hydroxy and other substituent groups.
[0070] The term "quaternary aromatic ammonium or phosphonium" as
used herein refers to a quaternary ammonium or phosphonium moiety
as referred to herein, in which the monomer contains an aromatic
moiety and a quarternary ammonium or phosphonium moiety, and in
which the quarternary ammonium or phosphonium moiety does not form
part of the aromatic ring. Examples of quaternary aromatic ammonium
salts include, but are not limited to, benzalkonium chlorides (such
as stearalkonium chloride, tetradecylammonium chloride),
benzoxonium chloride, domiphen bromide, tibezonium chloride,
benzethonium chloride, thonozium bromide, biphenium
hydroxynaphthoate, etc. Examples of quaternary aromatic phosphonium
salts include, but are not limited to, benzyltriphenylphosphonium
chloride, benzyltriphenylphosphonium bromide,
triphenyl-(3,4,5-trimethoxy-benzyl)-phosphonium bromide,
benzyltriethylphosphonium chloride, benzyltributylphosphonium
chloride, trimethylphenylphosphonium iodide,
dimethyldiphenylphosphonium iodide, ethyl triphenyl phosphonium
iodide, butyl triphenyl phosphonium bromide, methyl triphenyl
phosphonium bromide.
[0071] The term "quaternary cyclic aromatic ammonium or phosphonium
salt" as used herein refers to a quaternary ammonium moiety as
referred to herein, in which the monomer contains an aromatic
moiety and a quarternary ammonium moiety, in which the quarternary
ammonium moiety forms part of the aromatic ring. Examples of
quaternary cyclic aromatic ammonium salts include, but are not
limited to, acriflavinium chloride, cetylpyrdinium chloride,
chelerythrine, dequalinium, isometamidium chloride, ethidium
bromide, diquat, MPP+ (1-methyl-4-phenylpyridinium) etc.
[0072] The term "aryl" as used herein means a monocyclic, bicyclic
or tricyclic aromatic ring system containing, depending on the
number of atoms in the rings, for example from 6 to 14 carbon
atoms, and at least 1 aromatic ring and includes phenyl, naphthyl,
anthracenyl, 1,2-dihydronaphthyl, 1,2,3,4-tetrahydronaphthyl,
fluorenyl, indanyl, indenyl and the like.
[0073] The term "heteroaryl" or "heteroaromatic" as used herein
means a monocyclic, bicyclic or tricyclic ring system containing
one or two aromatic rings, and from 5 to 14 atoms, optionally 5 or
6 atoms, of which, unless otherwise specified, one, two, three,
four or five are a heteromoiety independently selected from N, NH,
NC.sub.1-6 alkyl, 0 and S and includes thienyl, furyl, pyrrolyl,
pyrididyl, indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl,
benzofuryl, benzothienyl and the like.
[0074] The term "(C.sub.1-C.sub.p)-alkyl" as used herein means
straight and/or branched chain, saturated alkyl radicals containing
from one to "p" carbon atoms and includes (depending on the
identity of p) methyl, ethyl, propyl, isopropyl, n-butyl, s-butyl,
isobutyl, t-butyl, 2,2-dimethylbutyl, n-pentyl, 2-methylpentyl,
3-methylpentyl, 4-methylpentyl, n-hexyl and the like, where the
variable p is an integer representing the largest number of carbon
atoms in the alkyl radical.
[0075] The term "(C.sub.2-C.sub.p)alkenyl" as used herein means
straight or branched chain, unsaturated alkyl groups containing
from two to p carbon atoms and one to three double bonds, and
includes (depending on the identity of p) vinyl, allyl,
2-methylprop-1-enyl, but-1-enyl, but-2-enyl, but-3-enyl,
2-methylbut-1-enyl, 2-methylpent-1-enyl, 4-methylpent-1-enyl,
4-methylpent-2-enyl, 2-methylpent-2-enyl, 4-methylpenta-1,3-dienyl,
hexen-1-yl and the like, where the variable p is an integer
representing the largest number of carbon atoms in the alkenyl
radical.
[0076] The term "(C.sub.2-C.sub.p)alkynyl" as used herein means
straight and/or branched chain, unsaturated alkyl groups containing
from one to n carbon atoms and one or more, suitably one to three,
triple bonds, and includes (depending on the identity of p)
ethynyl, 1-propynyl, 2-propynyl, 2-methylprop-1-ynyl, 1-butynyl,
2-butynyl, 3-butynyl, 1,3-butadiynyl, 3-methylbut-1-ynyl,
4-methylbut-ynyl, 4-methylbut-2-ynyl, 2-methylbut-1-ynyl,
1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1,3-pentadiynyl,
1,4-pentadiynyl, 3-methylpent-1-ynyl,
4-methylpent-2-ynyl4-methylpent-2-ynyl, 1-hexynyl and the like,
where the variable n is an integer representing the largest number
of carbon atoms in the alkynyl group.
[0077] The term "alkoxy" as used herein, alone or in combination,
refers to an alkyl ether radical, --O-alkyl, wherein the alkyl
group may be optionally substituted, and wherein the terms alkyl,
aliphatic and carbocyclyl are as defined herein. Non-limiting
examples of alkoxy radicals include methoxy, ethoxy, n-propoxy,
isopropoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy and the
like.
[0078] The term "counteranion" as used herein refers to a
negatively charged species consisting of a single element, or a
negatively charged species consisting of a group of elements
connected by ionic and/or covalent bonds. Examples of suitable
counteranions include, but are not limited to, the halides, for
example chloro or bromo.
[0079] The suffix "ene" added on to any of the above groups means
that the group is divalent, i.e. inserted between two other
groups.
[0080] The term "halo" or "halogen" as used herein means halogen
and includes chloro, fluoro, bromo and iodo.
(II) Detailed Description
[0081] The present disclosure relates to anti-microbial polymers,
which when in contact with the polymer, kill, inhibit and/or reduce
microbial growth, or prevent the growth of microbes, including
bacteria, fungi, viruses, protozoa, etc. The anti-microbial
polymers of the present disclosure are prepared from monomers
comprising a polymerizable cyclic moiety, in which the cyclic
moiety forms part of the polymer backbone. Such monomers may have
anti-microbial properties as the monomers themselves, or become
anti-microbial after polymerization, such that the anti-microbial
polymer has similar or greater anti-microbial properties than the
monomers alone.
[0082] In one embodiment therefore, the present disclosure includes
an anti-microbial polymer, comprising polymerizable units of [0083]
i) at least one monomer comprising a polymerizable cyclic moiety
wherein the cyclic moiety forms part of the polymer backbone, and
wherein the monomer further comprises an anti-microbial moiety.
[0084] In another embodiment, the present disclosure includes an
anti-microbial polymer, comprising polymerizable units of [0085] i)
at least one monomer comprising a polymerizable cyclic moiety
wherein the cyclic moiety forms part of the polymer backbone, and
wherein the monomer further comprises an anti-microbial moiety; and
[0086] ii) at least one unsaturated monomer having an ethylenically
unsaturated double or triple bond.
[0087] In one embodiment, the polymerizable cyclic moiety comprises
a radically polymerizable cyclic moiety.
[0088] In another embodiment, the polymerizable cyclic moiety
comprises an aromatic polymerizable cyclic moiety or a conjugated
polymerizable cyclic moiety. In one embodiment, the aromatic
polymerizable cyclic moiety or the conjugated polymerizable cyclic
moiety is unactivated.
[0089] In another embodiment, the anti-microbial moiety comprises a
quaternary ammonium moiety, a quaternary phosphonium moiety or a
moiety derived from quinones. In one embodiment, the at least one
monomer comprising a polymerizable cyclic moiety comprises a
quaternary aromatic ammonium or phosphonium salt, a quaternary
cyclic aromatic ammonium or phosphonium salt, or quinone or quinone
derivative.
[0090] In one embodiment, one monomer has at least one double or
triple bond.
[0091] In another embodiment of the disclosure, the quaternary
aromatic ammonium or phosphonium salt comprises a monomer of the
formula
##STR00001##
wherein Ar is optionally substituted (C.sub.6-C.sub.14)-aryl or
optionally substituted (C.sub.5-C.sub.14)-heteroaryl, Y is absent,
(C.sub.1-C.sub.10)-alkylene, (C.sub.2-C.sub.10)-alkenylene, or
(C.sub.2-C.sub.10)-alkynylene, wherein 1 or 2 carbon atoms are
optionally replaced with N, S or O; R.sub.1, R.sub.2 and R.sub.3
are independently or simultaneously optionally substituted H,
(C.sub.1-C.sub.24)-alkyl, (C.sub.2-C.sub.24)-alkenyl,
(C.sub.2-C.sub.24)-alkynyl, (C.sub.6-C.sub.14)-aryl,
(C.sub.5-C.sub.14)-heteroaryl or
(C.sub.1-C.sub.10)-alkylene-(C.sub.6-C.sub.14)-aryl, wherein the
optional substituents are chosen from one or more of halogen,
hydroxyl, (C.sub.1-C.sub.6)-alkyl, (C.sub.1-C.sub.6)-alkoxy,
thionyl, nitro, amino (--NH.sub.2), (C.sub.6-C.sub.14)-aryl or
(C.sub.5-C.sub.14)-heteroaryl, M is nitrogen or phosphorous, and X
is any suitable counteranion, such as halo.
[0092] In another embodiment, Ar is optionally substituted phenyl,
naphthyl, anthracenyl, 1,2-dihydronaphthyl,
1,2,3,4-tetrahydronaphthyl, fluorenyl, indanyl, indenyl, thienyl,
furyl, pyrrolyl, pyrididyl, indolyl, quinolyl, isoquinolyl,
tetrahydroquinolyl, benzofuryl, or benzothienyl. In one embodiment,
Ar is optionally substituted phenyl.
[0093] In another embodiment, Y is (C.sub.1-C.sub.6)-alkylene,
(C.sub.2-C.sub.6)-alkenylene, or (C.sub.2-C.sub.6)-alkynylene,
wherein 1 or 2 carbon atoms are optionally replaced with O,
optionally (C.sub.1-C.sub.6)-alkylene, in which one of the carbon
atoms is optionally replaced with O.
[0094] In a further embodiment, R.sub.1, R.sub.2 and R.sub.3 are
independently or simultaneously (C.sub.1-C.sub.24)-alkyl,
(C.sub.2-C.sub.24)-alkenyl, (C.sub.2-C.sub.24)-alkynyl, or
(C.sub.1-C.sub.10)-alkylene-(C.sub.6-C.sub.14)-aryl, optionally
(C.sub.1-C.sub.24)-alkyl or (C.sub.1-C.sub.20)-alkyl. In one
embodiment, R.sub.1, R.sub.2 and R.sub.3 are independently or
simultaneously (C.sub.1-C.sub.6)-alkylene-phenyl.
[0095] In one embodiment, the quaternary aromatic ammonium salt
comprises a monomer of the formula
##STR00002##
wherein Y' is (C.sub.1-C.sub.3)-alkylene, wherein 1 carbon atom is
optionally replaced with O; R.sub.1' and R.sub.2' are independently
or simultaneously (C.sub.1-C.sub.4)-alkyl optionally substituted
with --OH; R.sub.3' is (C.sub.1-C.sub.24)-alkyl or
(C.sub.1-C.sub.10)-alkylene-(C.sub.6-C.sub.14)-aryl, and R is one
or more optional substituents chosen from halogen,
(C.sub.1-C.sub.6)-alkyl, thionyl, nitro, (C.sub.6-C.sub.14)-aryl or
(C.sub.5-C.sub.14)-heteroaryl, and X is halo.
[0096] In one embodiment, Y is --CH.sub.2CH.sub.2O-- or
CH.sub.2.
[0097] In another embodiment, the quaternary aromatic ammonium salt
comprises a compound selected from
##STR00003##
[0098] In another embodiment, the quaternary aromatic ammonium salt
comprises a compound selected from
##STR00004##
[0099] In another embodiment, the quaternary aromatic phosphonium
salt comprises
##STR00005## ##STR00006##
[0100] In another embodiment of the disclosure, the quaternary
aromatic ammonium salt comprises a monomer of the formula
##STR00007##
wherein Ring B is an optionally substituted aromatic moiety
containing from 5 to 18 carbon atoms, in which from 0 to 4 carbon
atoms are replaced with a heteroatom selected from N, O and S,
R.sub.4 is H, (C.sub.1-C.sub.24)-alkyl, (C.sub.2-C.sub.24)-alkenyl,
(C.sub.2-C.sub.24)-alkynyl, (C.sub.6-C.sub.14)-aryl or
(C.sub.5-C.sub.14)-heteroaryl, wherein the optional substituents
are chosen from one or more of halogen, --OH,
(C.sub.1-C.sub.6)-alkoxy, thionyl, nitro, amino (--NH.sub.2),
(C.sub.6-C.sub.14)-aryl, (C.sub.5-C.sub.14)-heteroaryl, or two
adjacent substituents are joined to form a methylene dioxy moiety,
and X is any suitable counteranion, such as halo.
[0101] In one embodiment, Ring B is an optionally substituted
aromatic moiety containing from 5 to 14 carbon atoms, in which from
0 to 2 carbon atoms are replaced with a heteroatom selected from N,
O and S.
[0102] In one embodiment, R.sub.4 is H or (C.sub.1-C.sub.24)-alkyl,
such as --CH.sub.3, --CH.sub.2CH.sub.3 or --C.sub.16H.sub.33.
[0103] In another embodiment, the quaternary aromatic ammonium salt
comprises a monomer of the formula
##STR00008##
wherein R.sub.4 is H, (C.sub.1-C.sub.24)-alkyl,
(C.sub.2-C.sub.24)-alkenyl, (C.sub.2-C.sub.24)-alkynyl,
(C.sub.6-C.sub.14)-aryl or (C.sub.5-C.sub.14)-heteroaryl, R is one
or more optional substituents chosen from halogen, --OH,
(C.sub.1-C.sub.6)-alkyl, (C.sub.1-C.sub.6)-alkoxy, thionyl, nitro,
amino (--NH.sub.2), (C.sub.6-C.sub.14)-aryl,
(C.sub.5-C.sub.14)-heteroaryl, or two adjacent substituents are
joined to form a methylene dioxy moiety, and X is any suitable
counteranion, such as halo.
[0104] In one embodiment, R.sub.4 is H or (C.sub.1-C.sub.24)-alkyl,
such as --CH.sub.3, --CH.sub.2CH.sub.3 or --C.sub.16H.sub.33.
[0105] In one embodiment, the quaternary aromatic ammonium salt is
a monomer of the formula
##STR00009##
wherein R.sub.4 is H or (C.sub.1-C.sub.24)-alkyl, and X is any
suitable counteranion, such as halo.
[0106] In another embodiment, the quaternary aromatic ammonium salt
is
##STR00010##
[0107] In one embodiment, the quaternary aromatic ammonium salt
is
##STR00011##
[0108] In another embodiment of the disclosure, the quinone or
quinone derivative is a monomer of the formula
##STR00012##
R is one or more optional substituents chosen from halogen, OH,
(C.sub.1-C.sub.6)-alkyl, (C.sub.1-C.sub.6)-alkenyl,
(C.sub.1-C.sub.6)-alkoxy, thionyl, nitro, (C.sub.6-C.sub.14)-aryl,
(C.sub.5-C.sub.14)-heteroaryl, or two or more adjacent substituents
are joined together to form an optionally substituted aromatic or
non-aromatic monocyclic or polycyclic ring.
[0109] In one embodiment, quinone or quinone derivative is a
monomer of the formula
##STR00013##
[0110] In another embodiment of the disclosure, the at least one
monomer comprising a polymerizable cyclic moiety comprises
##STR00014## ##STR00015##
[0111] In one embodiment, the monomer comprising a polymerizable
cyclic moiety is present within the anti-microbial polymer at a
mole fraction of between 0.00001 to 0.99, or about 0.001 to about
0.90. In one embodiment, the mole fraction is between about 0.1 to
about 0.5, or about 0.2 to about 0.4, or about 0.2 to about 0.3. In
one embodiment, the monomer comprising a polymerizable cyclic
moiety is present as a mole fraction in the overall anti-microbial
polymer of about 0.20, or about 0.22, or about 0.23.
[0112] In another embodiment, the at least one unsaturated monomer
having an ethylenically unsaturated double or triple bond is any
monomer having such unsaturation which participates in the
polymerization reaction to form the anti-microbial polymers of the
present disclosure. Many ethylenically unsaturated monomers are
known to those skilled in the art.
[0113] In one embodiment, the at least one unsaturated monomer
having an ethylenically unsaturated double or triple bond comprises
[0114] (i) acrylic acid, acrylates and acrylate salts, such as
methacrylates; [0115] (ii) styrene and styrene derivatives; [0116]
(iii) vinylpyridines, such as 4-vinylpyridine, [0117] (iv)
acrylamides, [0118] (v) propylene, polypropylene and polypropylene
derivatives, [0119] (vi) ethylene, polyethylene and polyethylene
derivatives, [0120] (vii) vinylchlorides, [0121] (viii) alkenes and
alkynes, [0122] (ix) (C.sub.2-C.sub.20)-alkene, polyalkene,
(C.sub.2-C.sub.20)-alkyne and polyalkyne polyols, such as
polybutadiene diols and triols, polyisobutylene diols and triols,
polybutylene oxide diols and triols, such as 2-butyne-1,4-diol, or
cis-2-butene-1,4-diol; [0123] (x) aromatic polyols, such as
benzene-diol, benzene-1,2-dithiol, [0124] (xi) di-carboxylic acids,
such as maleic acid, fumaric acid, phthalic acid, glutaconic acid,
[0125] (xii) cellulose and cellulose derivatives, [0126] (xii)
vinyl acetate and vinyl acetate derivatives, [0127] (xiv) allyl
ethers, such as pentaerythritol allyl ether or allyl sucrose;
[0128] (xv) terpenes and terpenoids, such as linolool, citronellol,
or geraniol, [0129] (xvi) acrylated derivatives of epoxidized oils,
such as acrylated epoxidized soybean oil, [0130] (xvii) essential
oils or derivatives of plant oils containing polymerizable
components with an ethylenically unsaturated double or triple bond,
co-polymers thereof or polymers thereof, wherein any of the above
monomers are optionally fluoro-substituted.
[0131] In one embodiment, the at least one monomer having an
ethylenically unsaturated double or triple bond comprises acrylic
acid, acrylates, styrene, or a vinylpyridine. In one embodiment,
the at least one monomer having an ethylenically unsaturated double
or triple bond is vinyl acetate.
[0132] In another embodiment, the monomer comprises
##STR00016##
wherein M.sup.+ is any suitable counter-cation.
[0133] In another embodiment, the polymers of the present
disclosure comprise two or more different ethylenically unsaturated
monomers as defined above. For example, acrylic acid and styrene;
vinyl acetate and styrene; acrylic acid and pentaerythritol allyl
ether; acrylic acid and linalool; or acrylated epoxidized soybean
oil and linalool, may be used as combinations as the ethylenically
unsaturated monomers.
[0134] In one embodiment, the monomer comprising at least one
unsaturated monomer having an ethylenically unsaturated double or
triple bond is present within the anti-microbial polymer at a mole
fraction of between 0.00001 to 0.99, or about 0.001 to about 0.90.
In one embodiment, the mole fraction is between about 0.5 to about
0.9, or about 0.6 to about 0.9, or about 0.7 to about 0.9, or about
0.7 to about 0.8. In one embodiment, the monomer comprising a
polymerizable cyclic moiety is present as a mole fraction in the
overall anti-mcirobial polymer of about 0.70, or about 0.75, or
about 0.77, or about 0.78.
[0135] In one embodiment, the monomer comprising a polymerizable
cyclic moiety is present within the anti-microbial polymer.
[0136] In another embodiment of the disclosure, the anti-microbial
polymer comprises a polymer of the formula (I)
##STR00017##
wherein the monomer A is the at least one unsaturated monomer
having an ethylenically unsaturated double or triple bond as
defined in the present disclosure, the monomer B is the monomer
comprising a polymerizable cyclic moiety as defined in the present
disclosure, m, n and p are independently or simultaneously any
integers between 1 and 1,000,000.
[0137] In one embodiment, m and n are independently or
simultaneously integers between 1-10,000, or 1-1,000, or 1-500, or
1-100, or 1-10 or 1-5. In one embodiment, the properties of the
anti-microbial polymers of the present disclosure are modulated by
controlling the variables p, m and n. For example, the mechanical
and anti-microbial properties of the polymer are modulated by
varying m and n. In another embodiment, p is any integer between
1-100,000, or 1-50,000, or 1-10,000, or 1-1,000, or 1-500, or
1-100, or 1-10 or 1-5.
[0138] In one embodiment, the anti-microbial polymer comprises a
polymer of the formula (IA)
##STR00018##
wherein R.sub.1, R.sub.2 and R.sub.3 are as defined above, X is any
suitable counteranion, and m, n and p are independently or
simultaneously any integers between 1 and 1,000,000. In one
embodiment, R.sub.1 and R.sub.2 are methyl, and R.sub.3 is
(C.sub.8-C.sub.18)-alkyl, optionally, C.sub.8, C.sub.10, C.sub.12,
C.sub.14, C.sub.16, or C.sub.18, optionally, C.sub.14.
[0139] In one embodiment, m and n are independently or
simultaneously integers between 1-10,000, or 1-1,000, or 1-500, or
1-100, or 1-10 or 1-5. In one embodiment, the properties of the
anti-microbial polymers of the present disclosure are modulated by
controlling the variables m and n. In another embodiment, p is any
integer between 1-100,000, or 1-50,000, or 1-10,000, or 1-1,000, or
1-500, or 1-100, or 1-10 or 1-5.
[0140] In one embodiment, the anti-microbial polymer comprises a
polymer of the formula (IB)
##STR00019##
wherein R.sub.1, R.sub.2 and R.sub.3 are as defined above, X is any
suitable counteranion, and m, n and p are independently or
simultaneously integers between 1 and 1,000,000. In one embodiment,
R.sub.1 and R.sub.2 are methyl, and R.sub.3 is
(C.sub.8-C.sub.18)-alkyl, optionally, C.sub.8, C.sub.10, C.sub.12,
C.sub.14, C.sub.16, or C.sub.18, optionally, C.sub.14.
[0141] In one embodiment, m and n are independently or
simultaneously integers between 1-10,000, or 1-1,000, or 1-500, or
1-100, or 1-10 or 1-5. In one embodiment, the properties of the
anti-microbial polymers of the present disclosure are modulated by
controlling the variables m and n. In another embodiment, p is any
integer between 1-100,000, or 1-50,000, or 1-10,000, or 1-1,000, or
1-500, or 1-100, or 1-10 or 1-5.
[0142] In one embodiment, the anti-microbial polymer comprises a
polymer of the formula (IC)
##STR00020##
wherein R.sub.1, R.sub.2 and R.sub.3 are as defined above, X is any
suitable counteranion, and m, n and p are independently or
simultaneously integers between 1 and 1,000,000. In one embodiment,
R.sub.1 and R.sub.2 are methyl, and R.sub.3 is
(C.sub.8-C.sub.18)-alkyl, optionally, C.sub.8, C.sub.10, C.sub.12,
C.sub.14, C.sub.16, or C.sub.18, optionally, C.sub.14.
[0143] In one embodiment, m and n are independently or
simultaneously integers between 1-10,000, or 1-1,000, or 1-500, or
1-100, or 1-10 or 1-5. In one embodiment, the properties of the
anti-microbial polymers of the present disclosure are modulated by
controlling the variables m and n. In another embodiment, p is any
integer between 1-100,000, or 1-50,000, or 1-10,000, or 1-1,000, or
1-500, or 1-100, or 1-10 or 1-5.
[0144] In another embodiment of the disclosure, the anti-microbial
polymers are conjugated to cellulose or a cellulose derivative
either binding the cellulose sheets to each other or made in situ
with cellulose powder or cellulose waste.
[0145] In another embodiment of the disclosure, the monomers which
form the anti-microbial polymers of the present disclosure are
prepared in the presence of an ionic liquid. In one embodiment, the
ionic liquid is incorporated into the structure of the
anti-microbial polymer. In one embodiment, the ionic liquid is a
phosphonium ionic salt. In another embodiment, the phosphonium ion
salt has the structure
##STR00021##
[0146] wherein
[0147] each Z is independently or simultaneously
(C.sub.1-C.sub.20)-alkyl group or alkyl group with a single or
double bond and W is any suitable anionic ligand. The ionic liquid
serves as solvent, co-solvent, monomer and also contributes to
antimicrobial properties.
[0148] In another embodiment, each Z is independently or
simultaneously methyl, ethyl, propyl, butyl, isobutyl, pentyl,
hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl,
tetradecyl, pentadecyl or hexadecyl.
[0149] In another embodiment, W is chloride, bromide, decanoate,
(bis 2,4,4-trimethylpentyl)phosphinate, dicyanamide, tosylate,
methylsulfate, bistriflamide, hexafluorophosphate,
tetrafluoroborate, diethylphosphate or dedecylsulfonate.
[0150] In another embodiment of the disclosure, the at least one
unsaturated monomer having an ethylenically unsaturated double or
triple bond comprises a polyol or thiol having an ethylenically
unsaturated moiety, such as a polyalkene or polyalkyne polyol, such
as polybutadiene diol and triol, polyisobutylene diols and triols,
polybutylene oxide diols and triols, 2-butyne-1,4-diol, aromatic
polyols, such as benzene-diol, benzene-1,2-dithiol. The
anti-microbial polymers prepared from such diols results in a
polymer having pendant hydroxyl groups. In one embodiment, such
polymers are reacted with isocyanates such as an aromatic
di-isocyanate (toluene diisocyanate, methylene diphenyl
diisocyanate) to form modified polyurethane polymers which have
anti-microbial properties. Such anti-microbial polyurethane
derivatives are useful for preparing polyurethane articles having
anti-microbial properties, such as foam seating, medical devices,
catheters, coatings, adhesives, sealants and elastomers.
(IV) Processes for Preparation of the Disclosure
[0151] The polymers of the present disclosure are prepared using
techniques known to those skilled in the art.
[0152] In one embodiment, the polymers of the present disclosure
are prepared using techniques as described in US publication no.
2012-0049101. In one embodiment, the anti-microbial polymers of the
present disclosure are prepared in at least 95% yield, or about 98%
yield, or about 99% yield, or 100% yield. In one embodiment, there
are no by-products from the polymerization reaction to prepare the
polymers of the present disclosure. In one embodiment, all of the
reactants, including the monomers comprising a polymerizable cyclic
moiety and the unsaturated monomers having an ethylenically
unsaturated double or triple bond, and optionally the radical
initiators and ionic liquids, form part of the anti-microbial
polymers resulting in no waste products.
(IV) Uses of the Anti-Microbial Polymers
[0153] The anti-microbial polymers of the present disclosure are
useful to prevent or inhibit the growth of microbes, such as
bacteria, fungi, viruses and protozoa.
[0154] In one embodiment, the polymers are useful for the
preparation of devices comprised solely of the polymer itself, or
the polymer can form a coating on a device to impart anti-microbial
properties.
[0155] In one embodiment, the present disclosure includes an
anti-microbial medical device comprising, [0156] i) a medical
device; and [0157] ii) an anti-microbial polymer as defined in the
disclosure coated on the device.
[0158] In one embodiment, the device is selected from a catheter,
stent, wound dressing, contraceptive device, surgical implant,
orthopedic implant, dental implant, contact lens and replacement
joint.
[0159] In another embodiment, there is also included an
anti-microbial packaging material comprising, [0160] i) a packaging
material, [0161] ii) an anti-microbial polymer as defined in the
disclosure coated on the material.
[0162] In one embodiment, the packaging material is a food
packaging material that is optionally used to store perishable
food
[0163] In another embodiment, the anti-microbial polymer of the
disclosure is conjugated with cellulose or a cellulose derivative,
resulting in a pulp and paper product having anti-microbial
properties, wherein the pulp and paper product is, for example,
tissue paper, paper towel or toilet paper. Alternatively, in one
embodiment, the anti-microbial polymer of the disclosure is used as
a binder or glue, such as a laminating glue, in pulp and paper
products to bind the pulp and paper components together. For
example, the anti-microbial polymers of the present disclosure are
used as a laminating glue to bind plies of tissue paper, toilet
paper, and/or paper towel. In another embodiment, the
anti-microbial polymer is coated on the pulp and paper product.
[0164] In another embodiment, the anti-microbial polymer of the
present disclosure is coated on, or conjugated to, fabrics or other
materials to produce articles of clothing having anti-microbial
properties.
[0165] In another embodiment, the anti-microbial polymers of the
present disclosure are formed, for example by extrusion processing,
into specific objects or devices which therefore have inherent
anti-microbial properties. For example, the polymers of the present
disclosure are formed into a medical device such as a stent, a
construction material or consumer product. For example, the
polymers may be formed into a bathroom or kitchen object having
anti-microbial properties such as a sink, tap, tiles, countertop,
storage cabinets, flooring such as vinyl flooring.
[0166] In another embodiment, the anti-microbial polymers of the
disclosure may be formed into a polymer wood composite material
(for example, for decking), into parts of a marine vessel or ship,
fishnets or other marine aquaculture equipment. The polymers may
also be formed into a textile, or form part of a textile, such as
bedding, drapes, surgical masks, surgical gowns, etc.
[0167] In one embodiment, the anti-microbial polymers may be simply
sprayed on an object to impart anti-microbial properties to the
object. Alternatively, the polymers may be formed in situ with the
object.
[0168] In another embodiment, the anti-microbial polymers of the
present disclosure are also used in pharmaceutical and cosmetic
formulations and compositions, such as in intravenous solutions,
topical formulations, tablet and capsule formulations, to impart
anti-microbial properties to those formulations, especially against
gram positive bacteria, gram negative bacteria, yeast and
filamentous fungi. In one embodiment, the cosmetic formulation is
an anti-microbial soap, a personal care product, cosmetics, hand
sanitizers, and anti-microbial hydrogels.
[0169] In another embodiment, the anti-microbial polymers of the
present disclosure are formulated into cleaning solutions, as well
as sanitizers.
[0170] The operation of the disclosure is illustrated by the
following representative examples. As is apparent to those skilled
in the art, many of the details of the examples may be changed
while still practicing the disclosure described herein.
(IV) Examples
Example 1--Preparation of Anti-Microbial Polymer Using Acrylic Acid
and Benzyldimethyltetradecylammonium Chloride
[0171] In a three neck flask, 8 ml of Acrylic Acid (PAA) and 12 g
of Benzyldimethyltetradecylammonium chloride (Bz) were mixed under
magnetic stirring and gentle heating (less than 60.degree. C.)
until the Bz was completely dissolved in AA. The mixture was then
heated to 60.degree. C. and the heat was turned off, but magnetic
stirring continued. 0.5 g of the initiator
2,2'-Azobis(2-methylpropionitrile) (AIBN) was immediately added to
the reaction mixture and the polymerization was initiated. The
resulting reaction is schematically depicted below in Scheme I
below, showing the reaction and product of the PAA-BZ
polymerization, where m, n and p may be equal or an integer between
1 and 1,000,000 and R represents a long alkyl chain, in this
particular reaction R is a C14H29 alkyl chain. As the reaction is
exothermic, the temperature of the mixture continued to rise until
the reaction was complete and only solid polymer remains.
Alternatively the reaction can also be performed wherein the AIBN
is added to the initial mixture of BZ and AA, and once BZ and AIBN
are completely dissolved into the PAA, the solution can be heated
to 60.degree. C. to initiate the polymerization reaction. The
resulting polymer was characterized by nuclear magnetic resonance
spectroscopy (NMR) (FIG. 1), Fourier transform infra-red
spectroscopy (FTIR) (FIG. 2.) and ultra-violet-visible spectroscopy
(UV/Vs) (FIG. 3).
##STR00022##
Example 2--Preparation of Anti-Microbial Polymer Using Acrylic Acid
and Benzyldimethyltetradecylammonium Chloride and Cellulose
[0172] In a three neck flask, 8 ml of Acrylic Acid (PAA) and 12 g
of Benzyldimethyltetradecylammonium chloride (BZ) and 0.03 g
cellulose (CELL) were mixed under magnetic stirring and gentle
heating (less than 60.degree. C.) until the BZ was completely
dissolved in AA. The mixture was then heated to 60.degree. C. and
the heat was turned off, but magnetic stirring continues. 0.5 g of
the initiator 2,2'-Azobis(2-methylpropionitrile) (AIBN) was
immediately added to the reaction mixture and the polymerization
was initiated. As the reaction is exothermic, the temperature of
the mixture continued to rise until the reaction was complete and
only solid polymer remains. Alternatively the reaction can also be
performed wherein the AIBN is added to the initial mixture of CELL,
BZ and PAA, and once BZ and AIBN are completely dissolved into the
AA, the solution can be heated to 60.degree. C. to initiate the
polymerization reaction. Alternatively polymerization can be
initiated using hydrogen peroxide (H.sub.2O.sub.2) as an initiator.
The polymer of PAA-BZ-CELL was characterized by FTIR spectroscopy
(FIG. 4), and X-ray Diffraction (XRD) (FIG. 5) spectrum confirming
the presence of cellulose within the polymeric material. A proposed
structure speculating the interactions between the three components
(PAA, BZ and CELL) of the materials is presented in Scheme II, as
shown below, showing the structure of the purported interactions
between the three components (PAA, BZ and CELL) of the material
PAA-BZ-CELL, where A- is any counterion for the quaternary ammonium
compound. In this instance A- is a chlorine atom Cl-, and m, n and
p, q may be equal or an integer between 1 and 1,000,000.
##STR00023##
[0173] Alternatively, varying the ratios of cellulose to acrylic
acid while not varying the amount of BZ added were also examined
using the synthesis scheme described above where water is used as a
reaction solvent. These variations in the reactant concentrations
and the product yield are presented below in Tables 1 and 2.
Example 3--Preparation of Anti-Microbial Polymer Composed of Sodium
Acrylate and Benzyldimethyltetradecylammonium Chloride
[0174] PAA-BZ as previously synthesized was dissolved in water at a
high concentration (0.22 g/ml). A solution of 6M sodium hydroxide
(NaOH) was then slowly added drop wise into the dissolved solution
of PAA-BZ forming a solid polymeric precipitate, which is the
Sodium polyacrylate form (NAPAA) of the PAA-BZ polymer to form
NAPAA-BZ. This precipitate was characterized by FTIR (FIG. 6). The
polymer was then dissolved in Dimethylformamide (DMF) and a UV/Vis
spectrum of the sample was taken (FIG. 7). The proposed reaction
scheme of the product is similar to that of PAA-BZ with the final
product being depicted below in Scheme III, showing the reaction
product of the PAA-BZ+NaOH to form NAPAA-BZ, where m, n and p may
be equal or an integer between 1 and 1,000,000 and R represents a
long alkyl chain, in this particular reaction R is a C14H29 alkyl
chain. This salt form of the product can also be made using other
counterions on the acrylic acid such as lithium, potassium and
ammonium cations, based upon the choice of base used to react with
the PAA-BZ polymer.
##STR00024##
Example 4--Preparation of Anti-Microbial Polymer Using
Vinyl-Pyridine and Benzyldimethyltetradecylammonium Chloride and
Cellulose
[0175] In a three neck flask, 8 ml of 4-Vinylpyridine (PVP) and 8 g
of Benzyldimethyltetradecylammonium chloride (BZ) and 0.4 g
cellulose (CELL) were mixed under magnetic stirring and gentle
heating (less than 60.degree. C.) until the BZ was completely
dissolved in PVP. The mixture was then heated to 65.degree. C. and
the heat was turned off, but magnetic stirring continues. 1.2 g of
the initiator 2,2'-Azobis(2-methylpropionitrile) (AIBN) was
immediately added to the reaction mixture and the polymerization
was initiated. As the reaction was exothermic, the temperature of
the mixture continues to rise until the reaction is complete and
only solid polymer remains. Alternatively the reaction can also be
performed wherein the AIBN is added to the initial mixture of CELL,
BZ and PVP, and once BZ and AIBN are completely dissolved into the
PVP, the solution can be heated to 65.degree. C. to initiate the
polymerization reaction. A proposed structure speculating the
interactions between the three components (PAA, BZ and CELL) of the
materials is presented in Scheme 4, showing purported interactions
between the three components (PAA, BZ and CELL) of the material
PAA-BZ-CELL, where A- is any counterion for the quaternary ammonium
compound. In this instance A- is a chlorine atom Cl-, and m, n and
p, q may be equal or an integer between 1 and 1,000,000 An FTIR
spectrum of the PVP-BZ (High) sample is shown in FIG. 8.
##STR00025##
Example 5--Preparation of Anti-Microbial Polymer Using
Vinyl-Pyridine and Benzyldimethyltetradecylammonium Chloride and
Cellulose
[0176] In a three neck flask, 8 ml of 4-Vinylpyridine (PVP) and 2 g
of Benzyldimethyltetradecylammonium chloride (BZ) and 0.4 g
cellulose (CELL) were mixed under magnetic stirring and gentle
heating (less than 60.degree. C.) until the BZ was completely
dissolved in PVP. The mixture was then heated to 65.degree. C. and
the heat was turned off, but magnetic stirring continues. 1.2 g of
the initiator 2,2'-Azobis(2-methylpropionitrile) (AIBN was is
immediately added to the reaction mixture and the polymerization
was initiated. As the reaction was exothermic, the temperature of
the mixture continued to rise until the reaction was complete and
only solid polymer remains. Alternatively the reaction can also be
performed wherein the AIBN is added to the initial mixture of CELL,
BZ and PVP, and once BZ and AIBN are completely dissolved into the
PVP, the solution can be heated to 65.degree. C. to initiate the
polymerization reaction. The resulting reaction is schematically
similar to that depicted in scheme IV. An NMR spectrum of the
PVP-BZ polymer is presented in FIG. 9, an FTIR spectrum of the
PVP-BZ (low) sample is shown in FIG. 10 and a UV-Vis spectrum of
the polymer is shown in FIG. 11.
Example 6--Preparation of Anti-Microbial Polymer Using
Vinyl-Pyridine and Benzyldimethyltetradecylammonium Chloride and
Cellulose
[0177] In a three neck flask, 2 ml of 4-Vinylpyridine (PVP) and 1 g
of Benzyldimethyltetradecylammonium chloride (BZ) and were mixed
under magnetic stirring and gentle heating (less than 60.degree.
C.) until the BZ was completely dissolved in PVP. The mixture was
then heated to 65.degree. C. and the heat was turned off, but
magnetic stirring continues. 0.3 g of the initiator
2,2'-Azobis(2-methylpropionitrile) (AIBN) was immediately added to
the reaction mixture and the polymerization was initiated. As the
reaction was exothermic, the temperature of the mixture continued
to rise until the reaction was complete and only solid polymer
remains. Alternatively the reaction can also be performed wherein
the AIBN is added to the initial mixture of CELL, BZ and PVP, and
once BZ and AIBN are completely dissolved into the PVP, the
solution can be heated to 65.degree. C. to initiate the
polymerization reaction. The resulting reaction is schematically
shown in Scheme 5, showing reaction and products of the PVP-BZ
(Med) polymerization, where m, n and p may be equal or an integer
between 1 and 1,000,000 and R represents a long alkyl chain, in
this particular reaction R is a C14H29 alkyl chain. An FTIR
spectrum of the PVP-BZ (Med) sample is shown in FIG. 12 and a
UV-Vis spectrum of the polymer is shown in FIG. 13.
##STR00026##
Example 7--Preparation of Anti-Microbial Polymer Using Acrylic
Acid, Vinyl Pyridine and Benzyldimethyltetradecylammonium
Chloride
[0178] In a three neck flask, 9 ml of Acrylic Acid (PAA) and 1 ml
of 4-Vinylpyridine (PVP) and 2 g of
Benzyldimethyltetradecylammonium chloride (BZ) and were mixed under
magnetic stirring and gentle heating (less than 60.degree. C.)
until the BZ was completely dissolved in PAA and PVP mixture. The
mixture was then heated to 80.degree. C. and the heat is turned
off, but magnetic stirring continues. 0.6 g of the initiator
2,2'-Azobis(2-methylpropionitrile) (AIBN) was immediately added to
the reaction mixture and the polymerization was initiated. As the
reaction is exothermic, the temperature of the mixture continued to
rise until the reaction was complete and only solid polymer
remains. Alternatively the reaction can also be performed wherein
the AIBN is added to the initial mixture of CELL, BZ and PVP, and
once BZ and AIBN are completely dissolved into the PVP, the
solution can be heated to 80.degree. C. to initiate the
polymerization reaction. Some of the combinations in which the PAA,
PVP and BZ react to form random polymeric chains or crosslinked
products as reaction products in Scheme 6, in which m, n, o, p and
q can be equal to each other or integers from 1 to 1,000,000. A is
the counter ion in this instance it is Cl.sup.-, and X is any
substitution on the benzyl ring and in this instance is an H, and
B, C, C' and B' are monomers of the copolymer, in this instance
they optionally represent PVP or AA monomers, oligomers or
polymers. An NMR spectrum of the PAA-PVP-BZ sample is shown in FIG.
14.
##STR00027##
Example 8--Preparation of Anti-Microbial Polymer Crystals Using
Acrylic Acid, and Benzyldimethyltetradecylammonium Chloride
[0179] In a three neck flask, 0.125 g AIBN, 3.0 g BZ+2.0 g PAA+26.0
mL H.sub.2O (water) were mixed under magnetic stirring and gentle
heating (less than 60.degree. C.) until the BZ and AIBN and PAA was
completely dissolved. The mixture was then heated to 80.degree. C.
for two hours. The heat as then turned off and the mixture was
allowed to cool at room temperature over time. When the sample was
bottled in sample vials and allowed to sit overnight,
crystallization of the polymer was observed. An NMR spectrum of the
PAA-BZ+H2O product is presented in FIG. 15. The reaction scheme is
schematically similar to that depicted in Scheme 1.
Example 9--Viscosity Measurements
[0180] Viscosity measurements were taken of some of the polymers
synthesized and are presented below in Tables 3-8. The measurements
were taken using a Brookfield Synchro-lectric viscometer model LVF,
the values are reported in centi-poise (mPa*s, m=milli) and
calculated based as per the specifications set out by the
instrument manufacturer.
Example 10A--Thermogravimetric Analysis
[0181] The PAA-BZ polymer was tested using thermogravimetric
analysis (TGA) (FIG. 15) and differential scanning calorimetry
(DSC) (FIG. 16). The PAA-BZ+H2O crystals were also tested using DSC
(FIG. 17). The results of these tests are presented in FIGS. 15-17
respectively. The TGA demonstrates this polymer's thermal stability
up to 200.degree. C. making it amenable to extrusion, molding and
other processing techniques or applications below that
temperature.
Example 10B--Free Radical Studies Using uSR
[0182] The free radical intermediates from addition to Bz were
studied using .mu.SR technique at M20 beam line. Some of the
signals for formed free radicals are presented in FIGS. 18 to 22.
These results suggest that the initial free radical (such as
muonium) is added to the para position of the benzyl group within
the benzylammonium chloride molecule for the polymerization
reaction. This radical addition is schematically depicted below in
below.
##STR00028##
[0183] As shown by FIG. 23, when additional compounds (e.g. acrylic
acid or an alcohol) are added even at very low concentration, the
radical formation is enhanced and under some conditions a liquid
crystal is formed that leads to an antimicrobial polymeric liquid
crystal after free radical formation. Such liquid crystalline
polymeric materials with anti-microbial properties have
applications in optical sensors that detect or identify bacteria or
the presence of biological materials.
Example 11--Preparation of Anti-Microbial Homopolymer of
Benzylalkylammonium Chloride
[0184] 0.99 g of benzalkonium chloride (C14) was heated and stirred
in a round bottom flask. When the temperature reached 115.degree.
C., 0.33 mL of 30% hydrogen peroxide solution was added to the
flask. The heat was left on and the solution began boiling, with
the temperature increasing until it reached 175.degree. C. after 23
minutes. The solution slowly turned pale yellow then darkened to
orange and then a dark brown liquid. After 32 minutes the heat was
turned off. Upon cooling the product thickened to a very viscous
liquid and became a light brown soft semi-solid. The reaction is
schematically shown in Scheme 7, showing products of the BZ
homopolymerization, where p is an integer between 1 and 1,000,000
and R represents a long alkyl chain, in this particular reaction R
is a C14H29 alkyl chain, A is a suitable counter-ion, in this
particular reaction A is a chloride anion, and X is any
substitution on the benzyl ring and in this instance is an H. An
FTIR, .sup.1H and .sup.13C NMR spectrum of the product is shown in
FIGS. 24, 25 and 26, respectively.
##STR00029##
Example 12--Preparation of Anti-Microbial Polymer Using
2-Butyne-1,4-diol and Benzyldimethyltetradecylammonium Chloride
[0185] In a three neck flask, 0.7 g of 2-Butyne-1,4-diol (BYOL) and
3 g of Benzyldimethyltetradecylammonium chloride (BZ) were mixed
under magnetic stirring and gentle heating until the BZ was
completely melted, and the solution mixed to form a clear-yellow
solution. The mixture was then heated to 120.degree. C. and the
heat was turned off, but magnetic stirring continued. 0.09 g of the
initiator 2,2'-Azobis(2-methylpropionitrile) (AIBN) was immediately
added to the reaction mixture and the polymerization was initiated.
As the reaction is exothermic, the temperature of the mixture
continued to rise until the reaction was complete. After
approximately 15 minutes the reaction was stopped, and the blood
orange like dark red product solution was collected (yield 2.81 g).
The product is a viscous sticky liquid, which crystallizes within
an hour in the sample vial it is transferred to. This reaction was
also carried out with different initiator and monomer
concentrations using the same procedure and experimental conditions
described above where the concentrations were changed to (0.7 g
BYOL, 3 g BZ and 0.19 g AIBN) or using (3 g Bz, 2.39 g ByOL and
0.13 g AIBN). These varied conditions also produced orange to red
colored liquid polymers that crystallized after polymerization. The
reaction products are schematically depicted in Scheme 8, showing
products of the polymerization reaction, where m, q and p are
integers between 1 and 1,000,000, optionally q maybe 0, and R
represents a long alkyl chain, in this particular reaction R is a
C14H29 alkyl chain, A is a suitable counter-ion, in this particular
reaction A is a chloride anion, and C is the monomer of the
co-polymer, in this particular reaction it is 2-Butyne-1,4-diol. An
FTIR, of the product is shown in FIG. 27.
##STR00030##
Example 13--Preparation of Anti-Microbial Polymer Using
cis-2-Butene-1,4-diol and Benzyldimethyltetradecylammonium
Chloride
[0186] In a three neck flask, 0.67 ml of cis-2-Butene-1,4-diol
(BEOL) and 3 g of Benzyldimethyltetradecylammonium chloride (BZ)
were mixed under magnetic stirring and gentle heating until the BZ
was completely melted, and the solution mixed to form a
clear-yellow solution. The mixture was then heated to 100.degree.
C. and the heat as turned off, but magnetic stirring continued.
0.09 g of the initiator 2,2'-Azobis(2-methylpropionitrile) (AIBN)
was immediately added to the reaction mixture and the
polymerization was initiated. As the reaction is exothermic, the
temperature of the mixture continued to rise until the reaction was
complete. After approximately 10 minutes the reaction was stopped,
and the clear to yellow viscous liquid was collected (yield 2.74
g). This reaction was also carried out with different initiator and
monomer concentrations using the same procedure and experimental
conditions described above where the concentrations were changed to
(0.6 ml BEOL, 3 g BZ and 0.18 g AIBN) or using (3.01 g Bz, 2.28 ml
BEOL and 0.14 g AIBN). These varied conditions also produced a
clear to yellowish viscous liquid product. The reaction products
are similar to those schematically depicted in Scheme 8, where in
this particular reaction R is a C14H29 alkyl chain, A is a chloride
anion, and C in this particular reaction is cis-2-Butene-1,4-diol.
An FTIR, spectrum of the product is presented in FIG. 28.
Example 14--Preparation of Anti-Microbial Polymer Using Styrene and
Benzyldimethyltetradecylammonium Chloride
[0187] In a three neck flask, 3.18 ml of styrene (STY) and 3 g of
Benzyldimethyltetradecylammonium chloride (BZ) were mixed under
magnetic stirring and gentle heating until the BZ was completely
melted, and the solution mixed to form a clear solution. The
mixture was then heated to 70.degree. C. and the heat was turned
off, but magnetic stirring continued. 0.15 g of the initiator
2,2'-Azobis(2-methylpropionitrile) (AIBN) was immediately added to
the reaction mixture and the polymerization was initiated. After
approximately 30 minutes the reaction was stopped, and the
yellowish, white solid product was collected (yield 3.08 g). This
reaction was also carried out with different initiator and monomer
concentrations as well as temperatures at which the initiator was
added using the same procedure and experimental conditions
described above where the concentrations were changed to (3.18 ml
STY, 3 g BZ and 0.07 g AIBN added at 90.degree. C.) or using (3.18
ml STY, 3 g BZ and 0.15 g AIBN added at 90.degree. C.). These
varied conditions also produced a clear to yellow to white solid
polymeric product. The reaction products are similar to those
schematically depicted in Scheme 8, where in this particular
reaction R is a C14H29 alkyl chain, A is a chloride anion, and C in
this particular reaction is styrene. An FTIR, of the product is
presented in FIG. 29.
Example 15--Preparation of Anti-Microbial Polymer Using Vinyl
Acetate and Benzyldimethyltetradecylammonium Chloride
[0188] In a three neck flask, 2.56 ml of vinyl acetate (VA) and 3 g
of Benzyldimethyltetradecylammonium chloride (BZ) were mixed under
magnetic stirring and gentle heating until the BZ was completely
melted, and the solution mixed to form a clear solution. The
mixture was then heated to 63.degree. C. and the heat was turned
off, but magnetic stirring continued. 0.15 g of the initiator
2,2'-Azobis(2-methylpropionitrile) (AIBN) was immediately added to
the reaction mixture and the polymerization was initiated. After
approximately 20 minutes the reaction was stopped, and the product,
which was lemon-merengue like in color and a thick paste, was
collected. This reaction was also carried out with different
initiator and monomer concentrations using the same procedure and
experimental conditions described above where the concentrations
were changed to (2.56 ml VA, 3 g BZ and 0.28 g AIBN) or using (2.65
ml VA, 3 g BZ and 0.06 g AIBN). These varied conditions also
produced light yellow to off-white, thick paste like solid
polymeric products. The reaction products are similar to those
schematically depicted in Scheme 8, where in this particular
reaction R is a C14H29 alkyl chain, A is is a chloride anion, and C
in this particular reaction is vinyl acetate. An FTIR, .sup.1H and
.sup.13C NMR spectrum of the product is shown in FIGS. 30, 31 and
32 respectively.
Example 16--Preparation of Anti-Microbial Polymer Using Styrene,
Acrylic Acid and Benzyldimethyltetradecylammonium Chloride
[0189] In a three neck flask, 0.95 ml of Acrylic Acid (AA), 1.59 ml
Styrene (STY) and 3 g of Benzyldimethyltetradecylammonium chloride
(BZ) and were mixed under magnetic stirring and gentle heating
until the BZ was completely melted, and the solution mixed to form
a clear solution. The mixture was then heated to 98.degree. C. and
the heat wasis turned off, but magnetic stirring continues. 0.14 g
of the initiator 2,2'-Azobis(2-methylpropionitrile) (AIBN) was
immediately added to the reaction mixture and the polymerization
was initiated. After approximately 15 minutes the reaction was
stopped, and the product, which is clear, and sticky (glue-like)
was collected (yield 2.45 g). This reaction was also carried out
with different initiator and monomer concentrations using the same
procedure and experimental conditions described above where the
concentrations were changed to (2.8 ml STY, 0.56 ml AA, 3 g BZ and
0.15 g AIBN) or using (0.94 ml STY, 1.67 ml AA, 3 g BZ and 0.14 g
AIBN). These varied conditions also produced clear, sticky
polymeric products. The reaction products are similar to those
schematically depicted in Scheme 6, where in this particular
reaction R is a C14H29 alkyl chain, A is a chloride anion, and B,
C, C' and B' are monomers of the copolymer, in this instance they
optionally represent STY or AA monomers, oligomers or polymers. An
FTIR spectrum of the product is presented in FIG. 33.
Example 17--Preparation of Anti-Microbial Polymer Using Vinyl
Acetate, Acrylic Acid and Benzyldimethyltetradecylammonium
Chloride
[0190] In a three neck flask, 0.56 ml of Acrylic Acid (AA), 2.26 ml
Vinyl Acetate (VA) and 3 g of Benzyldimethyltetradecylammonium
chloride (BZ) and were mixed under magnetic stirring and gentle
heating until the BZ was completely melted, and the solution mixed
to form a clear solution. The mixture was then heated to 65.degree.
C. and the heat was turned off, but magnetic stirring continues.
0.14 g of the initiator 2,2'-Azobis(2-methylpropionitrile) (AIBN)
was immediately added to the reaction mixture and the
polymerization was initiated. After approximately 15 minutes the
reaction is stopped, and the product, which is an opaque-white,
soft polymeric solid was collected (yield 3.27 g). This reaction
was also carried out with different initiator and monomer
concentrations using the same procedure and experimental conditions
described above where the concentrations were changed to (0.75 ml
VA, 1.67 ml AA, 3 g BZ and 0.14 g AIBN) producing a compressible,
but more sturdy white polymer. The reaction products are similar to
those schematically depicted in Scheme 6, where in this particular
reaction R is a C14H29 alkyl chain, A is a chloride anion, and B,
C, C' and B' are monomers of the copolymer, in this instance they
optionally represent VA or AA monomers, oligomers or polymers. An
FTIR, .sup.1H and .sup.13C NMR spectrum of the product is presented
in FIGS. 34,35 and 36 respectively.
Example 18--Preparation of Anti-Microbial Polymer Using Acrylic
Acid, Pentaerythritol Allyl Ether and
Benzyldimethyltetradecylammonium Chloride
[0191] In a three neck flask 5.00 mL of acrylic acid (AA), 7.5 g of
benzyldimethyltetradecylammonium chloride (BZ), and 0.1849 mL of
70% pentaerythritol allyl ether (APE) were added to a 100 mL beaker
equipped with a thermometer and stir bar. The solution was stirred
and heated to 70.degree. C., at which point 0.319 g AIBN was added
to initiate polymerization. The reaction is quick and exothermic,
yielding 10.48 g (82% yield) of a cross-linked PAA-BZ-APE polymer.
An FTIR, spectrum of the product is presented in FIG. 37.
Example 19--Preparation of Anti-Microbial Polymer Using Acrylic
Acid, Linalool and Benzyldimethyltetradecylammonium Chloride
[0192] In a three neck flask 1 ml of Linalool (LIN), 0.214 ml of
acrylic acid (AA) and 0.97 g of benzyldimethyltetradecylammonium
chloride (BZ), were mixed under magnetic stirring and gentle
heating until the BZ was completely melted, and the solution mixed
to form a clear solution. The solution was then heated to
110.degree. C., and 0.73 ml of 30% hydrogen peroxide solution
(H.sub.2O.sub.2) was added, with the heat and stirring left on.
Upon the addition of H.sub.2O.sub.2 the temperature dropped to
90.degree. C. but within 30 seconds rose back up to 110.degree. C.
The temperature continued to rise and the solution began to turn
yellow, then orange and darkened. The temperature reached a high of
150.degree. C. after 24 minutes and stayed at this temperature for
another 16 minutes when the heat as turned off and the product
collected. The final product is a very viscous orange/brown liquid.
The reaction products are similar to those schematically depicted
in Scheme 6, where in this particular reaction R is a C14H29 alkyl
chain, A is a chloride anion, and B, C, C' and B' are monomers of
the copolymer, in this instance they optionally represent LIN
monomers or AA monomers, oligomers or polymers. An FTIR, .sup.1H
and .sup.13C NMR spectrum of the product is presented in FIGS. 38,
39 and 40 respectively.
Example 20--Preparation of Anti-Microbial Polymer Using Soybean Oil
Epoxidized Acrylate, Linalool, and Benzyldimethyltetradecylammonium
Chloride
[0193] In a three neck flask 2 ml of Linalool (LIN), 2.06 ml of
Soybean oil, epoxidized acrylate (EASO) and 2 g of
benzyldimethyltetradecylammonium chloride (BZ), were mixed under
magnetic stirring and gentle heating until the BZ was completely
melted, and the solution mixed to form a clear solution. The
solution was then heated to 110.degree. C., and 2 ml of 30%
hydrogen peroxide solution (H.sub.2O.sub.2) was added, with the
heat and stirring left on. Upon the addition of H.sub.2O.sub.2 the
temperature dropped down to 85.degree. C. and after 10 minutes the
temperature increased to 110.degree. C. and the solution was
boiling gently. The solution reached a maximum of 180.degree. C.
and started turning brown after 20 minutes when the heat was turned
off, and the product left to cool down to room temperature. The
final product is a patchy brown/white soft solid that is gel-like
in nature. An FTIR, .sup.1H and .sup.13C NMR spectrum of the
product is presented in FIGS. 41, 42 and 43 respectively.
Example 21--Preparation of Anti-Microbial Polymer Using Linalool,
and Benzyldimethyltetradecylammonium Chloride
[0194] In a three neck flask 1 ml of Linalool (LIN), and 1.93 g of
benzyldimethyltetradecylammonium chloride (BZ), were mixed under
magnetic stirring and gentle heating until the BZ was completely
melted, and the solution mixed to form a clear solution. The
solution was then heated to 110.degree. C., and 0.93 ml of 30%
hydrogen peroxide solution (H.sub.2O.sub.2) was added, with the
heat and stirring left on. Upon addition of H.sub.2O.sub.2 the
temperature decreased to 85.degree. C. and the only visible changes
were gentle boiling. As the solution continued to be heated it
began to turn yellow and continued to darken to brown. The
temperature reached a high of 180.degree. C. after 16 minutes and
then began to fall. After 17 minutes the heat was turned off and
upon cooling became a very viscous brown liquid. The reaction
products are similar to those schematically depicted in Scheme 8,
where in this particular reaction R is a C14H29 alkyl chain, A is a
chloride anion, and C in this particular reaction is linalool. An
FTIR, .sup.1H and .sup.13C NMR spectrum of the product is presented
in FIGS. 44, 45 and 46 respectively.
Example 22--Anti-Microbial Activity
Antibacterial Preliminary Susceptibility Testing Protocol
[0195] Compounds were tested for antibacterial activity, as
described in Ma et al. (2011), against pure cultures of Escherichia
coli, Pseudomonas aeruginosa, Bacillus cereus, Proteus
mirabilis/hauseri, and Staphylococcus aureus, supplied by Ward's
Natural Science Ltd. (St. Catherines, Ontario, Canada). All
cultures were maintained on Tryptic Soy agar. These cultures were
then transferred using an inoculation loop to 10 mL of Tryptic soy
broth, and grown at 37.degree. C. for 24 hours. Triplicates of
plate and broth cultures were made in case of error or
contamination.
[0196] Using a sterile swab, and aseptic techniques, the bacterial
broth inocula were transferred to Mueller-Hinton plates and spread
evenly, ensuring that the entire surface was inoculated. They were
then left to dry for 3-5 minutes.
[0197] The following control discs were used: Penicillin (10
.mu.g), Tetracycline (30 .mu.g), Chloramphenicol (30 .mu.g), and
Ampicillin (10 .mu.g). Four antibiotic discs containing different
compounds were placed equidistant from each other on a
Mueller-Hinton plate. Each compound had four replicates per
species.
[0198] Plates were incubated for 18-24 hrs at 37.degree. C., and
then observed for rings of inhibition. If clear rings of inhibition
were present, the diameter was measured twice using a caliper.
Absence of rings of inhibition indicated a failed test, meaning the
compound does not show enough antibacterial activity to be used in
further testing.
Preparation of Novel Compound Discs
[0199] Each novel compound was applied to sterile filter paper
discs as a solution (15 mg of compound in 3 mL of solvent). Each
disc received 20 .mu.L of solution, and was allowed to dry, giving
a final concentration of 100 .mu.g of compound per disc.
Protocol for Antimicrobial Susceptibility Testing on Filamentous
Fungi and Yeasts
[0200] Adapted from Messer et al., (2007), this protocol was used
to test novel compounds for antifungal properties against yeasts
and fungi. Compounds were tested for antifungal activity against
pure cultures of Saccharomyces cerevisiae, Candida albicans
supplied by Ward's Natural Science Ltd. and Aspergillus niger and
Aspergillus fumigatus supplied by Alere Inc. (Inverness Medical,
Ottawa, Ontario, Canada). All cultures were maintained on Sabouraud
agar. The cultures of S. cerevisiae, and C. albicans were
transferred, using an inoculation loop, to Erlenmeyer flasks
containing 100 mL of Malt Yeast Extract Broth, and grown with
shaking at 15.degree. C. for 48 hrs. The cultures of A. niger and
A. fumigatus were transferred, using an inoculation loop, to new
Sabouraud agar and grown for 48 hrs. at 27.degree. C., and
35.degree. C. respectively, to cause sporulation. Triplicates of
all the plates and broth cultures were made in case of error or
contamination.
[0201] Using a sterile swab, and aseptic techniques, the cell
suspension of S. cerevisiae, and C. albicans were transferred to
Sabouraud agar plates and spread evenly, ensuring that the entire
surface was inoculated. They were then left to dry for 10 minutes.
The plates containing A. niger and A. fumigatus were covered with 5
mL of 0.85% saline solution, which by using aseptic technique was
transferred to 10 mL of 0.85% of saline solution containing 0.2%
Tween 80. The 0.2% Tween 80 reduces the hydrophobicity of the
conidia, allowing the spores to be readily suspended (Messer et
al., 2007). Alternatively two small circles containing fungal
growth of the A Niger or A Fumigatus fungi were cut from the agar
plates, and using a glass/PTFE tissue homoginzer, were mixed and
homogenized with 5 ml of sterile MilliQ water to create a
suspension of fungal spores. Using a sterile swab, and aseptic
techniques, the spore inocula of A. niger and A. fumigatus were
transferred to Sabouraud agar plates and spread evenly, ensuring
that the entire surface was inoculated. They were then left to dry
for 10 minutes.
[0202] Amphotericin B (100 .mu.g) in acetone was used as a control.
Four antibiotic discs containing different compounds were place
equidistant apart on each Sabouraud plate. Each compound had four
replicates per species.
[0203] Plates containing S. cerevisiae, and C. albicans were
incubated for 18-24 hrs at 37.degree. C., A. niger for 48 hrs at
room temperature, and A. fumigatus for 18-24 hrs at 35.degree. C.
After incubation, the plates were observed for rings of inhibition.
If clear rings of inhibition were present, the diameter was
measured twice using a caliper. Halos indicated partial inhibition
of growth (Hicks et al., 2008). Absence of a ring of inhibition
constitutes a failed test, meaning the compound did not show enough
antifungal activity to be used in further testing.
Antibiotic Disk Susceptibility Testing Results
[0204] 1. Poly Acrylic Acid in Methanol
[0205] 2. PVP-CELL-BZ (High) in CHCl.sub.3
[0206] 3. PAA-BZ in THF
[0207] 4. PAA-CELL-BZ in THF
[0208] 5. PAA-BZ+H2O in Methanol
[0209] 6. PAA-PVP-BZ in H.sub.2O
[0210] 7. PVP-BZ in CDCl3
[0211] 8. PVP-CELL-BZ (Low) in CHCl3
[0212] 9. Penicillin (P 10 ug)
[0213] 10. Tetracycline (Te 30 ug)
[0214] 11. Chloramphenicol (C 30 ug)
[0215] 12. Ampicillin (AM 10 ug)
[0216] 13. Amphotericin B (Yeasts 50 ug/Filamentous 100 ug).
[0217] 14. Amphotericin B (20 .mu.g)
[0218] 15. Benzyldimethyltetradecylammonium chloride, (BZ) in
acetone
[0219] 16. BYOL-BZ in THF (am18)
[0220] 17. BEOL-Bz in THF (am16)
[0221] 18. STY-BZ in THF (AM2)
[0222] 19. VA-BZ in THF (am3)
[0223] 20. LIN-BZ in THF
[0224] 21. LIN-BZ-AA
[0225] 22. BZ homopolymer
[0226] The results of the above-noted compounds are shown in Tables
9 and 10.
Example 23--Preparation of Anti-Microbial Paper Towels
[0227] First, antimicrobial polymers of acrylic acid and benzyl
dimethyl alkyl ammonium chloride (C8-18) were prepared using the
procedure described in example 1 with hydrogen peroxide used as the
initiator, and benzyl dimethyl alkyl (C8-18) ammonium chloride used
instead of benzyldimethyltetradecylammonium chloride. This solution
is referred to as PAA-Bz-H
[0228] A 30% weight glue solution of the resulting polymer was
prepared by mixing the antimicrobial polymer with distilled water.
The glue solution was then sprayed on the sheets of 2 ply white
paper towels at various add-on rates of 100, 125, 150, 250 and 350
mg/ft.sup.2 respectively. The paper towels were then allowed to
dry.
[0229] After, 5 cm from each edge of the paper towels was cut out
(to prevent edge areas where spraying might have been irregular
being tested), and from the remaining paper towels, a single hole
punch machine was used to punch 6 mm paper discs from each of the
paper towels. These discs were then tested for anti-microbial
activity as per the protocol described in example 24 and the
results summarized in Tables 11 and 12.
Example 24--Toxicity Testing of Antimicrobial Polymers
[0230] The environmental toxicity of the antimicrobial paper towel
wipes, were characterized, by performing a rapidtoxkit test by
Microbiotests Inc, using the Thamnocephalus platyurus
crustacean.
[0231] The samples were prepared by weighing and then dissolving 1
2 ply sheet of each of the paper towels of interest (150 and 350
mg/ft.sup.2) and Cascades.RTM. anti-microbial paper towels
containing benzalkonium chloride as the active ingredient, in 1 L
of EPA moderate-hard synthetic freshwater prepared as per EPA
guidelines (Methods for Measuring the Acute Toxicity of Effluents
and Receiving Waters to Freshwater and Marine Organisms, 2002). The
samples were then diluted using the EPA moderate-hard synthetic
freshwater to a concentration of 200 .mu.g/L of initial paper towel
weight in solution. Additionally samples of the polymeric
antimicrobial solution used to prepare the paper towels (from
example 23), PAA-Bz-H, were also dissolved in the EPA moderate-hard
synthetic freshwater and diluted to concentrations of 2, 20, 60 and
200 .mu.g/L for the tests.
[0232] The rapid thamnocephalus test was carried out as per the
standard operating procedure of the rapidtoxkit (Standard
Operational Procedure of the Rapidtoxkit, 2004). Briefly, larvae of
Thamnocephalus platyurus aged 30-45 h were exposed for 1 h to the
samples prepared above in comparison to a control. A suspension of
red microspheres was subsequently added for ingestion by the test
organisms for 30 min. The larvae were then killed by addition of a
fixative solution provided in the kit. The animals were collected
from the test tubes and transferred to an observation plate for
microscopical examination of the presence or absence of red
particles in the digestive tract. The larvae in the controls have a
digestive tract that is colored deeply red, whereas stressed
(intoxicated) larvae do not ingest any particles and have an empty
digestive tract. Some microspheres can, however, be taken up at the
highest test dilutions. The quantitative importance of the toxic
effects is rated by determination of the percentage of test biota
with colored digestive tracts in the test dilutions versus that in
the controls. The % inhibition of particle uptake of the various
samples were determined as per the instructions of the toxkit,
where a value at or below 30% is considered non-toxic, and anything
higher requires greater investigation into toxicity effects. The
results are summarized in table 13. The LC50 of the polymeric spray
solution was also calculated as 98.58 .mu.g/L, demonstrating that
at a spray add-on rate of 150 mg/ft.sup.2, the sample is close to
the non-toxic threshold, and even at higher add-on rates, lower
aquatic toxicity relative to the Cascades.RTM. anti-microbial
towels.
TABLE-US-00001 TABLE 1 Reactions varying the ratios of PAA and CELL
using 46 mL of H.sub.2O (water) as a solvent, 1 g of BZ, 4 ml of
Isopropanol and 0.3 g of AIBN in the reaction mixture PAA Cellulose
Yield Sample (mL) (g) Initiator (%) 1 1 0.25 AIBN 50 2 5 0.5 AIBN
85 3 5 0.25 AIBN 91 4 5 0.1 AIBN 87 5 5 0 AIBN 92 6 1 0.5
H.sub.2O.sub.2 30
TABLE-US-00002 TABLE 2 Reactions varying the ratios of PAA and CELL
using 50 mL of H.sub.2O (water) as a solvent, 1 g of BZ, and 0.3 g
of AIBN in the reaction mixture AA Cellulose Yield Sample (mL) (g)
Initiator (%) 1 1 0.5 AIBN 50 2 5 0.5 AIBN 85 3 5 0.25 AIBN 91 4 5
0.1 AIBN 87 5 5 0 AIBN 92 6 1 0.5 H.sub.2O.sub.2 30
TABLE-US-00003 TABLE 3 3.0 g BZ + 2.0 g PAA + 0.125 g AIBN + 20.0
mL H2O at 23.7 C. speed spindle reading Viscosity 6 4 0.95 950 12 4
1.8 900 30 4 4.4 880 60 4 8.9 890 avg 905
TABLE-US-00004 TABLE 4 3.0 g BZ + 2.0 g PAA + 0.125 g AIBN + 22.0
mL H2O at 24.0 C. speed spindle reading viscosity 6 4 0.2 200 6 4
0.2 200 6 4 0.2 200 avg 0.2 200 12 4 0.45 225 12 4 0.48 240 12 4
0.45 225 avg 0.46 230 30 4 1 200 30 4 1 200 30 4 1 200 avg 1 200 60
4 2.2 220 60 4 2.15 215 60 4 2.2 220 2.183333 218.3333
TABLE-US-00005 TABLE 5 3.0 g BZ + 2.0 g PAA + 0.125 g AIBN + 24.0
mL H2O at 24.0 C. speed spindle reading viscosity avg 30 4 0.45 90
30 4 0.5 100 30 4 0.45 90 avg 0.466667 93.33333 60 4 1 100 60 4 1
100 60 4 1 100 1 100
TABLE-US-00006 TABLE 6 3.0 g BZ + 2.0 g PAA + 0.125 g AIBN + 26.0
mL H2O at 23.8 C. speed spindle reading viscosity 30 3 0.8 32 30 3
0.8 32 30 3 0.75 30 avg 0.783333 31.33333 60 3 1.8 36 60 3 1.7 34
60 3 1.7 34 avg 60 3 1.8 36 1.75 35
TABLE-US-00007 TABLE 7 3.0 g BZ + 2.0 g PAA + 0.125 g AIBN + 26.0
mL H2O at 23.9 C. speed spindle reading viscosity 30 3 0.8 32 30 3
0.8 32 30 3 0.8 32 avg 0.8 32 60 3 1.8 36 60 3 1.8 36 60 3 1.8 36
avg 60 3 1.8 36 1.8 36
TABLE-US-00008 TABLE 8 viscosity and pH of solutions of PVP-BZ and
PAA-BZ with the values reported as an average of 5 measurements at
24 C. Sample and Concentration (g Viscosity per ml H.sub.2O) (cP)
pH PVP-BZ (High) (0.1333 g/ml) 21.5 5 PAA-BZ (0.222 g/ml) 888 2
PAA-BZ (0.044 g/ml) 5.2 2 PAA-BZ (0.022 g/ml) 5.2 2
TABLE-US-00009 TABLE 9 Antibacterial Results Gram- Gram+ P. P.
Compounds B. cereus S. aureus E. coli hauseri aeruginosa 1 -- -- --
-- -- 2 8.70 10.10 9.10 8.57 -- 3 9.10 10.20 8.92 8.74 -- 4 9.10
11.00 8.92 9.27 -- 5 -- 9.30 -- -- -- 6 8.40 9.30 8.39 -- -- 7
10.10 9.80 9.10 8.39 -- 8 12.70 9.80 9.10 8.22 -- 9 -- 31.50 15.91
11.00 -- 10 20.30 23.30 20.45 29.50 10.75 11 26.30 17.70 32.25
16.50 -- 12 13.50 28.80 17.13 19.00 -- 15 14.30 13.43 12.70 12.63
8.13 16 14.60 13.20 10.90 12.77 8.67 17 14.73 15.57 11.50 12.40
8.10 18 13.07 13.37 11.23 13.30 7.90 19 11.70 12.97 12.47 13.90
8.43 20 9.4 9.3 8.8 9.4 -- 21 11.7 7.8 8.1 18.3 9.0 22 7.9 7.3 8.7
8.3 8.1
TABLE-US-00010 TABLE 10 Antifungal Results Yeast Filamentous Fungi
Compounds C. albicans S. cerevisiae A. niger A. fumigatus 1 -- --
-- -- 2 9.18 9.56 8.04 -- 3 8.04 9.09 8.22 8.04 4 8.22 -- 8.04 -- 5
-- -- -- -- 6 -- 9.27 -- -- 7 8.65 9.27 -- -- 8 8.39 9.27 -- -- 13
9.35 8.39 17.86 11.19 14 11.00 10.80 8.80 7.80 15 7.48 11.33 10.97
8.13 16 9.27 11.07 9.90 9.00 17 10.13 11.50 9.53 9.80 18 9.73 9.67
8.97 7.90 19 9.93 10.90 9.10 8.93 20 8 14.5 8.7 12.6 21 7.93 7.6 --
9.8 22 8.67 10.6 -- 13.4
TABLE-US-00011 TABLE 11 Antibacterial Results of Antimicrobial
Paper Towels Gram- Gram+ P. P. Compounds B. cereus S. aureus E.
coli hauseri aeruginosa B1 - 100 mg/ft 10.5 11.7 8.0 15.3 10.3 B2-
125 mg/ft 15.7 18.5 6.8 8.7 15.0 B3-150 mg/ft 10.3 17.5 0.0 13.7
11.3 T4-250 mg/ft 12.7 15.5 8.1 14.7 12.7 B5-350 mg/ft 15.0 14.4
8.1 9.3 11.7 CS - Cascades 16.0 16.3 9.7 11.0 16.6 9 Penicillin --
31.5 15.91 11 -- (P 10 ug) 10 Tetracycline 20.3 23.3 20.45 29.5
10.75 (Te 30 ug) 11 Chlor- 26.3 17.7 32.25 16.5 -- amphenicol (C 30
ug) 12 Ampicillin 13.5 28.8 17.13 19 -- (AM 10 ug)
TABLE-US-00012 TABLE 12 Antifungal Results of Antimicrobial Paper
Towels Yeast Filamentous Fungi Compounds C. albicans S. cerevisiae
A. niger A. fumigatus B1 - 100 mg/ft 7.2 7.3 -- -- B2- 125 mg/ft --
8.6 -- 8.1 B3-150 mg/ft 7.6 7.7 -- -- T4-250 mg/ft 6.4 -- -- --
B5-350 mg/ft 8.2 9.6 -- 8.5 Cascades 8.2 8.4 -- 9.8 PAA-BZ-H 10.6
10.8 -- 15.8 (100 .mu.g of solution onto paper discs) Amphotericin
B 9.7 13.4 8.7 9.4 (20 ug) AMB 20
TABLE-US-00013 TABLE 13 % Inhibition of Particle Uptake from Toxkit
Testing % Inhibition of Sample Particle Uptake Cascades (200 mg/L)
84.85 150 mg/ft.sup.2 (200 mg/L) 31.82 350 mg/ft.sup.2 (200 mg/L)
39.39 PAA-Bz-H (200 ug/L) 48.86 PAA-Bz-H (20 ug/L) 45.45 PAA-Bz-H
(2 ug/L) 54.55 PAA-Bz-H (60 ug/L) 100.00
* * * * *