U.S. patent application number 09/850324 was filed with the patent office on 2003-02-13 for antimicrobial polymer.
Invention is credited to McDonald, William F., Taylor, Andrew C., Wright, Stacy C..
Application Number | 20030032765 09/850324 |
Document ID | / |
Family ID | 25307825 |
Filed Date | 2003-02-13 |
United States Patent
Application |
20030032765 |
Kind Code |
A1 |
McDonald, William F. ; et
al. |
February 13, 2003 |
Antimicrobial polymer
Abstract
A polymeric composition having antimicrobial properties and a
process for rendering the surface of a substrate antimicrobial are
disclosed. The polymeric composition comprises a crosslinked
chemical combination of (i) a polymer having amino group-containing
side chains along a backbone forming the polymer, (ii) an
antimicrobial agent selected from metals, metal alloys, metal
salts, metal complexes and mixtures thereof, and (iii) a
crosslinking agent containing functional groups capable of reacting
with the amino groups. In one example embodiment, the polymer is a
polyamide formed from a maleic anhydride or maleic acid ester
monomer and alkylamines thereby producing a polyamide having amino
substituted alkyl chains on one side of the polyamide backbone; the
crosslinking agent is a phosphine having the general formula
(A).sub.3P wherein A is hydroxyalkyl; and the metallic
antimicrobial agent is selected from chelated silver ions, silver
metal, chelated copper ions, copper metal, chelated zinc ions, zinc
metal and mixtures thereof.
Inventors: |
McDonald, William F.;
(Utica, OH) ; Wright, Stacy C.; (Flint, MI)
; Taylor, Andrew C.; (Ann Arbor, MI) |
Correspondence
Address: |
QUARLES & BRADY LLP
411 E. WISCONSIN AVENUE
SUITE 2040
MILWAUKEE
WI
53202-4497
US
|
Family ID: |
25307825 |
Appl. No.: |
09/850324 |
Filed: |
May 7, 2001 |
Current U.S.
Class: |
528/310 |
Current CPC
Class: |
A01N 59/16 20130101;
A61Q 19/00 20130101; A61Q 17/005 20130101; C08K 3/015 20180101;
A61K 8/88 20130101; C08K 3/08 20130101; A01N 59/16 20130101; C08K
3/24 20130101; A61K 2800/54 20130101; A01N 59/16 20130101; A01N
25/10 20130101; A61K 2800/58 20130101; A01N 25/10 20130101; A01N
25/34 20130101; A01N 2300/00 20130101; A01N 25/24 20130101; A01N
59/20 20130101 |
Class at
Publication: |
528/310 |
International
Class: |
C08G 069/08 |
Claims
What is claimed is:
1. A polymeric composition having antimicrobial properties, the
polymeric composition comprising: a crosslinked chemical
combination of (i) a polymer having side chains along a backbone
forming the polymer, at least two of the side chains containing an
amino group, (ii) an antimicrobial agent selected from metals,
metal alloys, metal salts, metal complexes and mixtures thereof,
and (iii) a crosslinking agent containing at least two functional
groups capable of reacting with the amino groups.
2. The polymeric composition of claim 1 wherein: the polymer is a
polyamide, and the polymer is synthesized by (i) reacting a monomer
selected from unsaturated carboxylic acids, esters of unsaturated
carboxylic acids, anhydrides of unsaturated carboxylic acids, and
mixtures thereof, and a first amine to form an intermediate
reaction product, wherein the first amine is selected from
RR.sub.1NH, RNH.sub.2, RR.sub.1NH.sub.2.sup.+, RNH.sub.3.sup.+ and
mixtures thereof, wherein R and R.sub.1 can be the same or
different and each contain between about 1 and 50 carbon atoms and
are optionally substituted with heteroatoms oxygen, nitrogen,
sulfur, and phosphorus and combinations thereof, and (ii) reacting
the intermediate reaction product and a second amine to form the
polyamide, wherein the second amine is selected from
R.sub.2R.sub.3NH, R.sub.2NH.sub.2, R.sub.2R.sub.3NH.sub.2.sup.+,
R.sub.2NH.sub.3.sup.+ and mixtures thereof, wherein R.sub.2 and
R.sub.3 can be the same or different and each contain between about
1 and 50 carbon atoms and are optionally substituted with
heteroatoms oxygen, nitrogen, sulfur, and phosphorus and
combinations thereof, wherein multiple of the R, R.sub.1, R.sub.2,
and R.sub.3 are in vertically aligned spaced relationship along a
backbone formed by the polyamide.
3. The polymeric composition of claim 2 wherein R and R.sub.1 are
alkyl.
4. The polymeric composition of claim 3 wherein the first amine is
tetradecylamine.
5. The polymeric composition of claim 2 wherein the second amine is
a polyalkylene polyamine.
6. The polymeric composition of claim 5 wherein the polyalkylene
polyamine is pentaethylenehexamine.
7. The polymeric composition of claim 2 wherein the monomer is
selected from unsaturated dicarboxylic acids, esters of unsaturated
dicarboxylic acids, anhydrides of unsaturated dicarboxylic acids,
and mixtures thereof.
8. The polymeric composition of claim 7 wherein the monomer is
selected from maleic anhydride, maleic acid esters, and mixtures
thereof.
9. The polymeric composition of claim 2 wherein the antimicrobial
agent is selected from chelated silver ions, silver metal, chelated
copper ions, copper metal, chelated zinc ions, zinc metal and
mixtures thereof.
10. The polymeric composition of claim 1 wherein: the polymer is a
polyamide, and the polymer is synthesized by (i) reacting an
.alpha.,.beta.-unsaturated lactone and a first amine to form an
intermediate reaction product, wherein the first amine is selected
from RR.sub.1NH, RNH.sub.2, RR,NH.sub.2.sup.+, RNH.sub.3.sup.+ and
mixtures thereof, wherein R and R.sub.1 can be the same or
different and each contain between about 1 and 50 carbon atoms and
are optionally substituted with heteroatoms oxygen, nitrogen,
sulfur, and phosphorus and combinations thereof, and (ii) reacting
the intermediate reaction product and a second amine to form the
polyamide, wherein the second amine is selected from
R.sub.2R.sub.3NH, R.sub.2NH.sub.2, R.sub.2R.sub.3NH.sub.2.s- up.+,
R.sub.2NH.sub.3.sup.+ and mixtures thereof, wherein R.sub.2 and
R.sub.3 can be the same or different and each contain between about
1 and 50 carbon atoms and are optionally substituted with
heteroatoms oxygen, nitrogen, sulfur, and phosphorus and
combinations thereof, wherein multiple of the R, R.sub.1, R.sub.2,
and R.sub.3 are in vertically aligned spaced relationship along a
backbone formed by the polyamide.
11. The polymeric composition of claim 10 wherein R and R.sub.1 are
alkyl.
12. The polymeric composition of claim 11 wherein the first amine
is tetradecylamine.
13. The polymeric composition of claim 10 wherein the second amine
is a polyalkylene polyamine.
14. The polymeric composition of claim 13 wherein the polyalkylene
polyamine is pentaethylenehexamine.
15. The polymeric composition of claim 10 wherein the lactone is
2(5H)-furanone.
16. The process of claim 10 wherein the antimicrobial agent is
selected from chelated silver ions, silver metal, chelated copper
ions, copper metal, chelated zinc ions, zinc metal and mixtures
thereof.
17. The polymeric composition of claim 1 wherein the crosslinking
agent is selected from the group consisting of phosphines having
the general formula (A).sub.3P, wherein A is hydroxyalkyl, and
mixtures thereof.
18. The polymeric composition of claim 17 wherein the crosslinking
agent is tris(hydroxymethyl)phosphine.
19. The polymeric composition of claim 1 wherein the antimicrobial
agent is selected from chelated silver ions, silver metal, chelated
copper ions, copper metal, chelated zinc ions, zinc metal and
mixtures thereof.
20. A polymeric composition having antimicrobial properties, the
polymeric composition comprising: (a) a first crosslinked chemical
combination of (i) a first polymer having side chains along a
backbone forming the first polymer, at least two of the side chains
containing an amino group, (ii) a first antimicrobial agent
selected from metals, metal alloys, metal salts, metal complexes
and mixtures thereof, and (iii) a first crosslinking agent
containing at least two functional groups capable of reacting with
the amino groups; and (b) a second crosslinked chemical combination
of (i) a second polymer having side chains along a backbone forming
the second polymer, at least two of the side chains containing an
amino group, (ii) a second antimicrobial agent selected from
metals, metal alloys, metal salts, metal complexes and mixtures
thereof, and (iii) a second crosslinking agent containing at least
two functional groups capable of reacting with the amino groups,
wherein the first antimicrobial agent and the second antimicrobial
agent are different.
21. The polymeric composition of claim 20 wherein: the first
polymer and the second polymer are a polyamide, and the polyamide
is synthesized by (i) reacting a monomer selected from unsaturated
carboxylic acids, esters of unsaturated carboxylic acids,
anhydrides of unsaturated carboxylic acids, and mixtures thereof,
and a first amine to form an intermediate reaction product, wherein
the first amine is selected from RR.sub.1NH, RNH.sub.2,
RR.sub.1NH.sub.2.sup.+, RNH.sub.3.sup.+ and mixtures thereof,
wherein R and R.sub.1 can be the same or different and each contain
between about 1 and 50 carbon atoms and are optionally substituted
with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and
combinations thereof, and (ii) reacting the intermediate reaction
product and a second amine to form the polyamide, wherein the
second amine is selected from R.sub.2R.sub.3NH, R.sub.2NH.sub.2,
R.sub.2R.sub.3NH.sub.2.sup.+, R.sub.2NH.sub.3.sup.+ and mixtures
thereof, wherein R.sub.2 and R.sub.3 can be the same or different
and each contain between about 1 and 50 carbon atoms and are
optionally substituted with heteroatoms oxygen, nitrogen, sulfur,
and phosphorus and combinations thereof, wherein multiple of the R,
R.sub.1, R.sub.2, and R.sub.3 are in vertically aligned spaced
relationship along a backbone formed by the polyamide.
22. The polymeric composition of claim 21 wherein: the first
crosslinking agent and the second crosslinking agent are selected
from the group consisting of phosphines having the general formula
(A).sub.3P, wherein A is hydroxyalkyl, and mixtures thereof.
23. The polymeric composition of claim 20 wherein: the first
antimicrobial agent is selected from chelated copper ions, copper
metal, and mixtures thereof, and the second antimicrobial is
selected from chelated silver ions, silver metal, and mixtures
thereof.
24. The polymeric composition of claim 20 wherein: the first
antimicrobial agent is selected from chelated copper ions, copper
metal, and mixtures thereof, and the second antimicrobial is
selected from chelated zinc ions, zinc metal, and mixtures
thereof.
25. The polymeric composition of claim 20 wherein: the first
polymer and the second polymer are a polyamide, and the polyamide
is synthesized by (i) reacting an .alpha.,.beta.-unsaturated
lactone and a first amine to form an intermediate reaction product,
wherein the first amine is selected from RR.sub.1NH, RNH.sub.2,
RR.sub.1NH.sub.2.sup.+, RNH.sub.3.sup.+ and mixtures thereof,
wherein R and R.sub.1 can be the same or different and each contain
between about 1 and 50 carbon atoms and are optionally substituted
with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and
combinations thereof, and (ii) reacting the intermediate reaction
product and a second amine to form the polyamide, wherein the
second amine is selected from R.sub.2R.sub.3NH, R.sub.2NH.sub.2,
R.sub.2R.sub.3NH.sub.2.sup.+, R.sub.2NH.sub.3.sup.+ and mixtures
thereof, wherein R.sub.2 and R.sub.3 can be the same or different
and each contain between about 1 and 50 carbon atoms and are
optionally substituted with heteroatoms oxygen, nitrogen, sulfur,
and phosphorus and combinations thereof, wherein multiple of the R,
R.sub.1, R.sub.2, and R.sub.3 are in vertically aligned spaced
relationship along a backbone formed by the polyamide.
26. A process for rendering the surface of a substrate
antimicrobial, the process comprising: (a) providing a polymer
having side chains along a backbone forming the polymer, at least
two of the side chains containing an amino group; (b) mixing the
polymer with a crosslinking agent and a metallic antimicrobial
agent selected from metals, metal alloys, metal salts, metal
complexes and mixtures thereof, to produce a polymer solution, the
crosslinking agent containing at least two crosslinking functional
groups capable of reacting with the amino groups; and (c) coating
at least a portion of the substrate with the polymer solution to
produce a crosslinked polymer coating on the substrate.
27. The process of claim 26 wherein the crosslinking agent is
selected from the group consisting of phosphines having the general
formula (A).sub.3P, wherein A is hydroxyalkyl, and mixtures
thereof.
28. The process of claim 27 wherein the crosslinking agent is
tris(hydroxymethyl)phosphine.
29. The process of claim 26 wherein the substrate comprises a
polymeric material selected from polyolefins, polyacrylics,
polyvinyl chloride, polyamides, polyurethanes, polyurethaneureas,
silicone urethane copolymers, polyvinylpyrrolidone, polyvinyl
alcohols, cellulosic materials, polystyrene, polyesters,
fluorinated polymers, silicone polymers, natural rubber,
polycarbonates, and mixtures thereof.
30. The process of claim 26 wherein the antimicrobial agent is
selected from chelated silver ions, silver metal, chelated copper
ions, copper metal, chelated zinc ions, zinc metal, and mixtures
thereof.
31. The process of claim 26 wherein: the polymer is a polyamide,
and step (a) comprises: (i) reacting a monomer selected from
unsaturated carboxylic acids, esters of unsaturated carboxylic
acids, anhydrides of unsaturated carboxylic acids, and mixtures
thereof, and a first amine to form an intermediate reaction
product, wherein the first amine is selected from RR.sub.1NH,
RNH.sub.2, RR.sub.1NH.sub.2.sup.+, RNH.sub.3.sup.+ and mixtures
thereof, wherein R and R.sub.1 can be the same or different and
each contain between about 1 and 50 carbon atoms and are optionally
substituted with heteroatoms oxygen, nitrogen, sulfur, and
phosphorus and combinations thereof; and (ii) reacting the
intermediate reaction product and a second amine to form the
polyamide, wherein the second amine is selected from
R.sub.2R.sub.3NH, R.sub.2NH.sub.2, R.sub.2R.sub.3NH.sub.2.sup.+,
R.sub.2NH.sub.3.sup.+ and mixtures thereof, wherein R.sub.2 and
R.sub.3 can be the same or different and each contain between about
1 and 50 carbon atoms and are optionally substituted with
heteroatoms oxygen, nitrogen, sulfur, and phosphorus and
combinations thereof, wherein multiple of the R, R.sub.1, R.sub.2,
and R.sub.3 are in vertically aligned spaced relationship along a
backbone formed by the polyamide.
32. The process of claim 31 wherein R and R.sub.1 are alkyl.
33. The process of claim 32 wherein the first amine is
tetradecylamine.
34. The process of claim 31 wherein the second amine is a
polyalkylene polyamine.
35. The process of claim 34 wherein the polyalkylene polyamine is
pentaethylenehexamine.
36. The process of claim 31 wherein the monomer is selected from
unsaturated dicarboxylic acids, esters of unsaturated dicarboxylic
acids, anhydrides of unsaturated dicarboxylic acids, and mixtures
thereof.
37. The process of claim 36 wherein the monomer is selected from
maleic anhydride, maleic acid esters, and mixtures thereof.
38. The process of claim 26 wherein: the polymer is a polyamide,
and step (a) comprises: (i) reacting an .alpha.,.beta.-unsaturated
lactone and a first amine to form an intermediate reaction product,
wherein the first amine is selected from RR.sub.1NH, RNH.sub.2,
RR.sub.1NH.sub.2.sup.+, RNH.sub.3.sup.+ and mixtures thereof,
wherein R and R.sub.1 can be the same or different and each contain
between about 1 and 50 carbon atoms and are optionally substituted
with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and
combinations thereof; and (ii) reacting the intermediate reaction
product and a second amine to form the polyamide, wherein the
second amine is selected from R.sub.2R.sub.3NH, R.sub.2NH.sub.2,
R.sub.2R.sub.3NH.sub.2.sup.+, R.sub.2NH.sub.3.sup.+ and mixtures
thereof, wherein R.sub.2 and R.sub.3 can be the same or different
and each contain between about 1 and 50 carbon atoms and are
optionally substituted with heteroatoms oxygen, nitrogen, sulfur,
and phosphorus and combinations thereof, wherein multiple of the R,
R.sub.1, R.sub.2, and R.sub.3 are in vertically aligned spaced
relationship along a backbone formed by the polyamide.
39. The process of claim 38 wherein R and R.sub.1 are alkyl.
40. The process of claim 39 wherein the first amine is
tetradecylamine.
41. The process of claim 38 wherein the second amine is a
polyalkylene polyamine.
42. The process of claim 41 wherein the polyalkylene polyamine is
pentaethylenehexamine.
43. The process of claim 38 wherein the lactone is 2(5H)-furanone.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] This invention relates to a polymeric composition having
antimicrobial properties and a process for rendering the surface of
a substrate antimicrobial. The polymeric composition is a
crosslinked chemical combination of (i) a polymer having amino
group-containing side chains along a backbone forming the polymer,
(ii) an antimicrobial agent selected from metals, metal alloys,
metal salts, and metal complexes, and (iii) a crosslinking agent
containing functional groups capable of reacting with the amino
groups on the polymer.
[0003] 2. Description of the Related Art
[0004] Many medical procedures involve the placement of medical
devices, such as catheters, endotracheal tubes, prostheses, grafts,
sutures, dressings and implants, in the human body. Infection is a
common complication associated with the use of such medical
devices. Accordingly, many research efforts have concentrated on
finding means to prevent infection associated with these medical
devices.
[0005] One solution to this infection problem has been the use of
medical device coatings having metallic antimicrobial agents. An
"antimicrobial" agent is an agent that has antiviral,
antibacterial, and/or antifungal properties. (Antiviral means
capable of killing, or suppressing the replication of, viruses.
Anti-bacterial means bacteriostatic or bactericidal. Bactericidal
means the killing of microorganisms. Bacteriostatic means
inhibiting the growth of microorganisms. Antifungal means capable
of killing or suppressing replication of fungi.) It has been
particularly desirable to use a coating for implantable medical
devices that is bacteriostatic, i.e., inhibits bacterial growth,
such that the device can be implanted for longer periods without
compromising the subject through a secondary bacterial infection.
For example, U.S. Pat. No. 4,054,139 discloses a catheter coated
with a silver-based material that reduces infection; U.S. Pat. No.
4,603,152 discloses a medical device coated with an antimicrobial
composition including a polymeric binder and an antimicrobial metal
compound such as a silver salt; U.S. Pat. No. 4,933,178 discloses a
medical device having an antimicrobial coating comprising a
polymeric material and a metal (e.g., silver, gold, zinc, platinum,
copper) salt of sulfonylurea; and U.S. Pat. No. 5,019,096 discloses
an infection resistant material used on medical devices which
includes a polymeric component (e.g., polyurethane or silicone) and
a silver salt.
[0006] Even though various medical device coatings having metallic
antimicrobial agents are known, there is still a need for an
improved antimicrobial polymer coating that may be easily applied
to a substrate to provide an article which has excellent
antimicrobial properties and which retains its antimicrobial
properties in a permanent and non-leachable fashion when in contact
with bodily fluids for prolonged periods. In addition, it would be
beneficial if this coating could be combined with an
anti-thrombogenic coating to prevent both clotting and bacterial
infection. There is also a need for antimicrobial coatings that are
useful in fields other than medical devices, such as antifouling
applications for aqueous and marine environments, and corrosion
control.
SUMMARY OF THE INVENTION
[0007] The foregoing needs are met by a polymeric composition
having antimicrobial properties, wherein the polymeric composition
comprises a crosslinked chemical combination of (i) a polymer
having side chains along a backbone forming the polymer, at least
two of the side chains containing an amino group, (ii) an
antimicrobial agent selected from metals, metal alloys, metal
salts, metal complexes and mixtures thereof, and (iii) a
crosslinking agent containing at least two functional groups
capable of reacting with the amino groups. An article according to
the invention comprises a substrate and a coating of the polymeric
composition disposed on at least a portion of the substrate.
[0008] The polymer used in the polymeric composition comprises a
polymer having side chains along a backbone forming the polymer
wherein at least two of the side chains contain an amino group (
--NRH, --NH.sub.2, --NRH.sub.2.sup.+, --NH.sub.3.sup.+). In one
example embodiment, the polymer is a polyamide having amino
substituted alkyl chains on one side of the polymer backbone. The
crosslinking agent used in the polymeric composition contains at
least two functional groups capable of reacting with the amino
groups of the polymer used in the coating. In one example of the
crosslinking agent used in the polymeric composition, the
crosslinking agent is selected from the group consisting of
phosphines having the general formula (A).sub.3P, wherein A is
hydroxyalkyl, and mixtures thereof. One more specific example of
the crosslinking agent used in the polymeric composition is
tris(hydroxymethyl)phosphine. Specific non-limiting examples of the
metallic antimicrobial agent used in the polymeric composition
include chelated silver ions, silver metal, chelated copper ions,
copper metal, chelated zinc ions, zinc metal and mixtures
thereof.
[0009] An article having an antimicrobial surface may be produced
by a process according to the invention in which a polymer having
at least two amino substituted side chains is mixed with a metallic
antimicrobial agent and a crosslinking agent to produce a polymer
solution. The crosslinking agent contains at least two crosslinking
functional groups which react and combine with amino groups on the
polymer. The polymer solution is coated on at least a portion of a
substrate to produce a crosslinked antimicrobial polymer coating on
the substrate.
[0010] In an example embodiment of the invention, the versatile
chemical methodology of the invention allows for the deposition of
an antimicrobial polymeric composition on a polymeric substrate
(e.g., polydimethylsiloxane, polyurethane, and polypropylene). The
polymeric composition includes a two dimensional polymer having a
backbone of repeating .beta.-amino acid units with long aliphatic
side-chain and free NH-- and NH.sub.2--substituents and may be
synthesized by condensation of 2(5H)-furanone, or maleic acid
derivatives (such as anhydride, esters, and so on) with a
long-chain amine (e.g., tetradecylamine) and a polyamine (e.g.,
pentaethylenehexamine). Crosslinking of the two-dimensional polymer
is undertaken with tris(hydroxymethyl)phosphine (the crosslinking
agent) and a metallic antimicrobial agent such as chelated silver
ions, silver metal, chelated copper ions, copper metal, chelated
zinc ions, and zinc metal.
[0011] Experimental studies indicate that when chelated silver
ions, silver metal, chelated copper ions, copper metal, chelated
zinc ions or zinc metal are incorporated into the two-dimensional
polymer and the polymer is crosslinked with the crosslinking agent,
the resulting polymeric composition exhibits strong inhibitory
activity against target pathogenic microorganisms. When the
polymeric composition comprises: (a) first crosslinked chemical
combination of (i) the polymer, (ii) a first antimicrobial agent
selected from metals, metal alloys, metal salts, and metal
complexes, and (iii) the crosslinking agent; and (b) a second
crosslinked chemical combination of (i) the polymer, (ii) a second
different antimicrobial agent selected from metals, metal alloys,
metal salts, and metal complexes, and (iii) the crosslinking agent,
a galvanic cell is formed between the two different metals or ions
that provides synergistic antimicrobial activity greater than the
sum of the activity of the individual metals or ions alone.
[0012] It is therefore an advantage of the present invention to
provide an improved antimicrobial polymeric composition that may be
easily applied to a substrate to produce an article which has
excellent antimicrobial properties and which retains its
antimicrobial properties in a permanent and non-leachable fashion
when placed in an environment (e.g., bodily fluids) that may
promote bacterial growth.
[0013] It is another advantage of the present invention to provide
an improved antimicrobial polymeric composition that may be easily
applied to a substrate for the prevention of medical device-related
infections.
[0014] It is a further advantage of the present invention to
provide an improved antimicrobial polymeric composition that may be
easily applied to a substrate along with an anti-thrombogenic
coating to prevent both clotting and bacterial infections.
[0015] It is yet another advantage of the present invention to
provide an improved antimicrobial polymeric composition that may be
easily applied to a substrate for antifouling applications for
aqueous and marine environments.
[0016] It is still another advantage of the present invention to
provide an improved antimicrobial polymeric composition that may be
easily applied to a substrate for corrosion control coatings.
[0017] These and other features, aspects, and advantages of the
present invention will become better understood upon consideration
of the following detailed description, drawings, and appended
claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1A shows a process for synthesizing a polyamide that is
suitable for forming an antimicrobial polymeric composition coating
in accordance with the present invention;
[0019] FIG. 1B shows example polyamides having amino groups that
are suitable for forming the antimicrobial polymeric composition
coating in accordance with the present invention; and
[0020] FIGS. 2A and 2B show a process for synthesizing another
example polyamide having amino groups that are suitable for forming
the antimicrobial polymeric composition coating in accordance with
the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0021] The present invention is directed to a polymeric composition
having antimicrobial properties. The polymeric composition
comprises a crosslinked chemical combination of (i) a polymer
having side chains along a backbone forming the polymer, at least
two of the side chains containing an amino group, (ii) an
antimicrobial agent selected from metals, metal alloys, metal
salts, metal complexes and mixtures thereof, and (iii) a
crosslinking agent containing at least two functional groups
capable of reacting with the amino groups. An article having a
antimicrobial surface according to the invention comprises a
substrate and a coating of the antimicrobial polymeric composition
disposed on at least a portion of the substrate.
[0022] The polymer used in the antimicrobial polymeric composition
comprises a polymer having side chains along a backbone forming the
polymer wherein at least two of the side chains contain an amino
group (--NRH, --NH.sub.2, --NRH.sub.2.sup.+, --NH.sub.3.sup.+). In
one example embodiment of the polymer, the polymer is a polyamide
synthesized using the polymerization reactions disclosed in U.S.
Pat. No. 6,153,724, which are shown in FIG. 1A. Looking at FIG. 1A,
it can be seen that the polyamide can be synthesized using an
.alpha.,.beta.-unsaturated gamma-lactone, such as 2(5H)-furanone,
as an agent to effect the regular, sequential alignment of side
chains along a polyamide backbone. The furanone undergoes facile
reaction with a primary amine by Michael-type addition to yield
.alpha.,.beta.-amino gamma-lactone which then polymerizes to form a
polyamide chain with the pendant side chain. Depending on the side
group (R), the method can produce many different types of
polyamides. When the R group is a polyamine (such as
pentaethylenehexamine), a polymer having alkyl chains on one side
and amino substituted alkyl chains on the other side of the polymer
backbone and hydroxymethyl groups on the other side of the backbone
is formed. See FIG. 1B. This example two-dimensional polymer has a
backbone of repeating .beta.-amino acid units with fatty alkyl
(tetradecyl) and polyamine (derived from pentaethylenehexamine)
side chains randomly distributed along the chain. By virtue of its
amphithetic properties, the two-dimensional polymers are easily
soluble in both water and most organic solvents (e.g., alcohols,
tetrahydrofuran, chloroform, toluene, N,N-dimethylformamide, and
the like).
[0023] One polyamide disclosed in U.S. Pat. No. 6,153,724 and
useful in the present invention is formed by reacting an
.alpha.,.beta.-unsaturated lactone and a first amine to form an
intermediate reaction product, wherein the first amine is selected
from RR.sub.1NH, RNH.sub.2, RR.sub.1NH.sub.2.sup.+, RNH.sub.3.sup.+
and mixtures thereof, wherein R and R.sub.1 can be the same or
different and each contain between about 1 and 50 carbon atoms and
are optionally substituted with heteroatoms oxygen, nitrogen,
sulfur, and phosphorus and combinations thereof; and (ii) reacting
the intermediate reaction product and a polyamine to form the
polyamide, wherein the second polyamine is selected from
R.sub.2R.sub.3NH, R.sub.2NH.sub.2, R.sub.2R.sub.3NH.sub.2.sup.+,
R.sub.2NH.sub.3.sup.+ and mixtures thereof, wherein R.sub.2 and
R.sub.3 can be the same or different and each contain an amino
group (--NRH, --NH.sub.2, --NRH.sub.2.sup.+, --NH.sub.3.sup.+) and
between about 1 and 50 carbon atoms and are optionally substituted
with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and
combinations thereof, wherein multiple of the R, R.sub.1, R.sub.2,
and R.sub.3 are in vertically aligned spaced relationship along a
backbone formed by the polyamide. In one example embodiment of the
invention, R, R.sub.1, R.sub.2, and R.sub.3 may be selected from
alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, hydroxyl,
nitrile, carboxyl, sulfate, phosphate, sulfonyl, trialkylammonium
and combinations thereof and optionally can be substituted with a
halogen selected from the group consisting of chlorine, iodine,
bromine, fluorine and combinations thereof. The R, R.sub.1,
R.sub.2, and R.sub.3 groups may be the same or different depending
on the desired structure for the final polyamide. In other words,
the first amine and the second amine used in the polymerization
process may be the same or different.
[0024] In another example of the polymer used in the antimicrobial
polymeric composition, the polymer is a polyamide synthesized using
the polymerization reaction disclosed in the U.S. patent
application entitled "Two Dimensional Polyamides Prepared from
Unsaturated Carboxylic Acids and Amines" filed on Oct. 27, 2000 by
William F. McDonald et al., which is owned by the assignee of the
present invention and is incorporated herein by reference. In the
U.S. patent application, there is described a polymerization
process in which a monomer selected from unsaturated carboxylic
acids, esters of unsaturated carboxylic acids, anhydrides of
unsaturated carboxylic acids, and mixtures thereof is reacted with
a first amine to form an intermediate reaction product, and then
the intermediate reaction product is reacted with a polyamine to
form a polyamide wherein at least a portion of the side chains
along a backbone forming the polyamide are amino substituted alkyl
chains. See FIGS. 2A and 2B (wherein R.sub.1 includes an amino
group). The process for producing this polyamide involves reacting
a monomer selected from unsaturated carboxylic acids, esters of
unsaturated carboxylic acids, anhydrides of unsaturated carboxylic
acids and mixtures thereof with a first amine to form an
intermediate reaction product in the reaction mixture, wherein the
first amine is selected from RR.sub.1NH, RNH.sub.2,
RR.sub.1NH.sub.2.sup.+, RNH.sub.3.sup.+ and mixtures thereof,
wherein R and R.sub.1 can be the same or different and each contain
between about 1 and 50 carbon atoms and are optionally substituted
with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and
combinations thereof. The reaction of the monomer and the first
amine forms an intermediate reaction product in the reaction
mixture. The intermediate reaction product is then reacted with a
second amine selected from R.sub.2R.sub.3NH, R.sub.2NH.sub.2,
R.sub.2R.sub.3NH.sub.2.sup.+, R.sub.2NH.sub.3.sup.+ and mixtures
thereof, wherein R.sub.2 and R.sub.3 can be the same or different
and each contain an amino group (--NRH, --NH.sub.2,
--NRH.sub.2.sup.+, --NH.sub.3.sup.+) and each contain between about
1 and 50 carbon atoms and are optionally substituted with
heteroatoms oxygen, nitrogen, sulfur, and phosphorus and
combinations thereof. The reaction of the intermediate reaction
product with the second amine forms the polyamide in the reaction
mixture. The polyamide may then be separated from the reaction
mixture. A polyamide produced in accordance with the method of the
invention includes multiples of the R, R.sub.1, R.sub.2, and
R.sub.3 groups in vertically aligned spaced relationships along a
backbone formed by the polyamide.
[0025] Suitable unsaturated carboxylic acids, esters of unsaturated
carboxylic acids, and anhydrides of unsaturated carboxylic acids
for use as the monomer in this polymerization process have for
example from 3 to 18 carbon atoms in the molecule. Of this group of
acids, the monocarboxylic acid, acrylic acid, and the dicarboxylic
acid, maleic acid, are preferred. Of this group of esters, maleic
acid monoesters are preferred. A non-limiting example of anhydrides
of the unsaturated carboxylic acids is maleic anhydride. In one
example embodiment of the invention, R, R.sub.1, R.sub.2, and
R.sub.3 may be selected from alkyl, alkenyl, alkynyl, cycloalkyl,
aryl, aralkyl, hydroxyl, nitrile, carboxyl, sulfate, phosphate,
sulfonyl, trialkylammonium and combinations thereof and optionally
can be substituted with a halogen selected from the group
consisting of chlorine, iodine, bromine, fluorine and combinations
thereof. The R, R.sub.1, R.sub.2, and R.sub.3 groups may be the
same or different depending on the desired structure for the final
polyamide. In other words, the first amine and the second amine
used in the polymerization process may be the same or
different.
[0026] The crosslinking agent used in the coating contains at least
two functional groups capable of reacting with the amino groups of
the polymer used in the coating. It has been discovered that the
polymer can be crosslinked using a phosphine crosslinking agent
having the general formula (A).sub.3P and mixtures thereof, wherein
A is hydroxyalkyl. The A groups of the phosphine crosslinking agent
undergo a spontaneous Mannich-type reaction with amino groups on
the polymer under mild conditions (pH.about.7, aqueous or organic
media, room temperature, 2-24 hours). This results in the formation
of an aminomethyl-phosphine linkage (N--CH.sub.2--P--CH.sub.2--N)
which is much less susceptible to enzyme deactivation and
hydrolysis at a low pH than other known crosslinkages. In addition,
the phosphine crosslinking agent offers the benefits of operational
simplicity, good biocompatibility, and low cost. The phosphine
crosslinking agent can also react with the substrate to create
tightly bound anchors between the polyamide coating and the
substrate. Non-limiting examples of phosphine crosslinking agents
include tris(hydroxymethyl)phosphine,
tris(1-hydroxyethyl)phosphine, and tris(1-hydroxypropyl)phosphine.
In certain circumstances, it may be cost effective to form the
phosphine crosslinking agent in situ such as by the reaction of
tetrakis-(hydroxymethyl)phosphonium chloride and triethylamine.
[0027] The amount of phosphine crosslinking agent and the amount of
polymer used to produce the antimicrobial polymeric composition can
be varied depending upon the particular crosslinking agent
utilized, the reaction conditions and the particular product
application contemplated. Typically, the ratio of A groups in the
phosphine crosslinking agent to the total of amount of amino groups
in the polyamide can be varied to achieve a predetermined level of
crosslinking. Typically, the A groups in the phosphine crosslinking
agent to the total of amount of amino groups in the polymer is
about 30% to provide acceptable crosslinking. In one version of the
invention, enough phosphine crosslinking agent is added to the
polyamide such that at least 30% of the available amino groups in
the polymer are crosslinked by the A groups in the phosphine
crosslinking agent. This percentage or amount of phosphine
crosslinker can be varied to obtain antimicrobial polymeric
composition coatings with the desired crosslink density.
[0028] The metallic antimicrobial agent used in the polymeric
composition may be selected from metals, metal alloys, metal salts,
metal complexes and mixtures thereof. Preferably, the metallic
antimicrobial agent is a metal, metal alloy, metal salt, metal
complex, or mixture thereof, which is bactericidal or
bacteriostatic. Non-limiting illustrative antimicrobial agents may
be selected from chelated silver ions, silver metal, chelated
copper ions, copper metal, chelated zinc ions, zinc metal, and
mixtures thereof. The amount and/or type of the antimicrobial agent
used will vary depending on the particular material employed and
ultimate desired effect. For instance, the amount and/or type of
the antimicrobial agent which is used in a particular application
may vary depending on the type and amount of contamination which is
likely to occur and the size of the antimicrobial surface present
in the article. For example, certain metals may be highly effective
against most bacteria, but less effective against other bacteria.
One example level of the antimicrobial agent is from about 4 grams
to 12 grams of silver salt to 1.0 to 1.5 grams of the polymeric
composition.
[0029] The antimicrobial polymeric composition may be applied to
any substrate that is considered useful in applications where
antimicrobial properties are advantageous. For instance, an article
having antimicrobial properties and useful as a medical device may
include a substrate comprising a polymeric material conventionally
used to fabricate articles commonly used in contact with bodily
fluids. In this example, suitable polymeric material may be
selected from polyolefins, polyacrylics, polyvinyl chloride,
polyamides, polyurethanes, polyurethaneureas, silicone urethane
copolymers, polyvinylpyrrolidone, polyvinyl alcohols, cellulosic
materials, polystyrene, polyesters, fluorinated polymers, silicone
polymers, natural rubber, polycarbonates, and mixtures thereof. The
particular substrate selected does not constitute a critical aspect
of the invention other than to serve as a support substrate for the
antimicrobial polymeric coating composition.
[0030] An article having a antimicrobial surface according to the
invention may be prepared generally as follows. First, the
substrate is precleaned, if necessary, and the surface of the
substrate is modified via coupling agent, if necessary. A solution
of the polymer having side chains along a backbone forming the
polymer wherein at least two of the side chains contain an amino
group (--NRH, --NH.sub.2, --NRH.sub.2.sup.+, --NH.sub.3.sup.+) is
then prepared in a suitable solvent, such as isopropanol. The
polymer concentration can vary and is typically from 1 to 5%
depending on the desired coating concentration and final volume of
antimicrobial coating desired. A metallic antimicrobial agent
selected from metals, metal alloys, metal salts, metal complexes
and mixtures thereof is then added to the polymer solution and
stirred until the metallic antimicrobial agent dissolves. Without
intending to be bound by theory, it is believed that the metal ions
form a complex with the polymer, which acts as a chelating agent.
The word "complex" indicates some form of bonding wherein the
antimicrobial agent is incorporated on, or with, the polymer in
such as manner to provide slow release of the antimicrobial
agent.
[0031] Once the metallic antimicrobial agent has completely
dissolved into the polymer solution, a crosslinking agent
containing at least two functional groups capable of reacting with
the amino groups of the polymer (e.g., tris(hydroxymethyl)phosphine
or intermediates which react to form tris(hydroxymethyl)phosphine)
is added. Care is taken not to heat this solution as premature
crosslinking is undesirable. The polymer/crosslinking
agent/metallic antimicrobial agent solution is applied to a
substrate and the substrate may be heated or baked in an oven at
125.degree. C. for four hours to complete the crosslinking process
and create a crosslinked antimicrobial polymeric composition
coating on the substrate. This step may be repeated if necessary.
Typically, the coatings are applied using a dipping process.
However, the coatings can be spin coated, brushed, sprayed,
sponged, or the like onto the substrate.
[0032] The reaction between the polyamide, the crosslinking agent,
and the metallic antimicrobial agent can be conducted in aqueous
and organic phases. Considering the solvent ability, the
compatibility with the substrate and reagents, the boiling point,
the miscibility with other solvents, and safety factors,
isopropanol is one preferred solvent for the coating procedure. In
order to provide a smooth crosslinking under optimum stoichiometry,
an example concentration ratio for the reactants is:
Polymer:Crosslinking Agent=1:0.15 w/w % to 1:0.4 w/w %. Higher
concentrations of tris(hydroxymethyl)phosphine may lead to an
extremely short pot life by precipitation of the crosslinked
materials from solution. Accordingly, a suitable concentration
ratio for the reactants is: Polymer: Crosslinking agent=1000
milligrams:440 milligrams.
EXAMPLES
[0033] The following examples serve to further illustrate the
invention. The Comparative Example details the preparation of a
substrate having a crosslinked polyamide coating. Examples 1-6
detail the preparation of substrates having different antimicrobial
crosslinked polyamide coatings in accordance with the invention.
The examples are not intended to limit the invention in any
way.
Comparative Example
[0034] Preparation of Substrates Having A Crosslinked Polyamide
Coating
[0035] A polymer with side chains was prepared as follows. First,
1.0 moles (144.1 grams) of maleic acid mono-ethyl ester was
dissolved in 100 grams of isopropanol in a break away resin kettle.
The kettle containing the maleic acid mono-ethyl ester/isopropanol
solution was then cooled in an ice bath with agitation. Second, 0.5
moles (160.7 grams) of commercially available tetradecylamine was
dissolved in 250 grams of isopropanol and added slowly to the
cooled maleic acid mono-ethyl ester solution with stirring. A
Michael-type addition reaction product began to precipitate within
5 minutes. The tetradecylamine addition required about two hours
with ice bath conditions being maintained throughout. Third, 58.1
grams (0.25 moles) of commercially available pentaethylenehexamine
were added drop wise to the reaction solution over a two hour
period. The reaction is removed from the ice bath at the end of the
monomer addition and stirred for an additional 2 hours. The amount
of pentaethylenehexamine charged is determined from the monomer
charge from the formation of intermediate. After complete addition
of the pentaethylene-hexamine, the reaction kettle was removed from
the cold bath with continuous stirring for another 2 hours. A 2.5%
solution of the polymer with side chains was then prepared in
isopropanol. One milliliter of triethylamine was then added to the
solution under stirring. Two milliliters of glutaraldehyde were
then added to the solution. A 0.15 milliliter portion of
tetrakis-(hydroxymethyl) phosphonium chloride was then added to the
solution followed by 0.3 milliliters of dioctyl sebacate. The
polymer solution was then applied to a 10 millimeter by 10
millimeter polydimethylsiloxane substrate and a 10 millimeter by 10
millimeter polypropylene substrate. In doing so, the substrates
were dipped into the polymer solution and removed after 0.5 to 2
minutes. Each wet substrate was dried and cured by hot air at
120.degree. C.-150.degree. C. for 1 minute. The dip-and-dry
operation can be repeated one or more times when a higher thickness
is required. The coated substrates were then placed in an oven at
125.degree. C. for four hours.
Example 1
[0036] Preparation of a Substrate with a Polyamide Coating
Including Silver
Example 1a
Preparation of A Polyamide with Side Chains
[0037] A polymer with side chains was prepared as follows. First,
1.0 moles (144.1 grams) of maleic acid mono-ethyl ester was
dissolved in 100 grams of isopropanol in a break away resin kettle.
The kettle containing the maleic acid mono-ethyl ester/isopropanol
solution was then cooled in an ice bath with agitation. Second, 0.5
moles (160.7 grams) of commercially available tetradecylamine was
dissolved in 250 grams of isopropanol and added slowly to the
cooled maleic acid mono-ethyl ester solution with stirring. A
Michael-type addition reaction product began to precipitate within
5 minutes. The tetradecylamine addition required about two hours
with ice bath conditions being maintained throughout. Third, 58.1
grams (0.25 moles) of commercially available pentaethylenehexamine
were added drop wise to the reaction solution over a two hour
period. The reaction is removed from the ice bath at the end of the
monomer addition and stirred for an additional 2 hours. The amount
of pentaethylene-hexamine charged is determined from the monomer
charge from the formation of intermediate. After complete addition
of the pentaethylene--hexamine, the reaction kettle was removed
from the cold bath with continuous stirring for another 2
hours.
Example 1b
Preparation of an Antimicrobial Polymer Solution from Example 1a
Polymer
[0038] A 2.5% solution of the polymer of Example 1a was prepared in
isopropanol. Then, 10 grams of silver pentaflouropropionate were
added to 50 milliliters of the 2.5% polymer solution. The solution
was then stirred until the silver pentaflouropropionate completely
dissolved. The solution darkened and became very dark brown or
black after 2 or 3 hours. One milliliter of triethylamine was then
added to the solution under stirring. Two milliliters of
glutaraldehyde were then added to the solution. A 0.15 milliliter
portion of tetrakis-(hydroxymethyl) phosphonium chloride was then
added to the solution followed by 0.3 milliliters of dioctyl
sebacate.
Example 1c
[0039] Preparation of a Substrate with an Antimicrobial Polymer
Coating
[0040] The polymer solution prepared in Example 1b was applied to a
10 millimeter by 10 millimeter polydimethylsiloxane substrate and a
10 millimeter by 10 millimeter polypropylene substrate. In doing
so, the substrates were dipped into the solution and removed after
0.5 to 2 minutes. Each wet substrate was dried and cured by hot air
at 120.degree. C.-150.degree. C. for 1 minute. The dip-and-dry
operation can be repeated one or more times when a higher thickness
is required. The coated substrates were then placed in an oven at
125.degree. C. for four hours.
Example 2
[0041] Preparation of a Substrate with Polyamide Coating Including
Copper
Example 2a
[0042] Preparation of A Polyamide with Side Chains
[0043] A polymer with side chains was prepared as detailed in
Example 1a.
Example 2b
Preparation of an Antimicrobial Polymer Solution from Example 2a
Polymer
[0044] A 10 gram sample of the polymer of Example 2a was dissolved
in isopropanol. Eight grams of copper 2-ethylhexanoate were then
added to the polymer solution, and the resulting polymer--copper
salt solution was stirred until it became a dark greenish brown
color in about 3 hours. It is believed that the color developed
from the green to aqua blue of the salt to form the dark
green/brown complex of the polymer with the copper ion. The
polymer-copper complex was rotovapped to dryness, and thereafter
rotovapped and dried in a vacuum oven to remove the last traces of
isopropanol. Two grams of the polymer-copper complex were then
added to 50 milliliters of a 2.5% solution of the polymer of
Example 2a in isopropanol. Seven grams of #200 mesh copper powder
were then added to the solution. One milliliter of triethylamine
was then added to the solution under stirring. Two milliliters of
glutaraldehyde were then added to the solution. A 0.2 milliliter
portion of tetrakis-(hydroxymethyl) phosphonium chloride was then
added to the solution followed by 0.2 milliliters of dioctyl
sebacate.
Example 2c
Preparation of a Substrate with an Antimicrobial Polymer
Coating
[0045] The polymer solution prepared in Example 2b was applied to a
10 millimeter by 10 millimeter polydimethylsiloxane substrate and a
10 millimeter by 10 millimeter polypropylene substrate. In doing
so, the substrates were dipped into the solution and removed after
0.5 to 2 minutes. Each wet substrate was dried and cured by hot air
at 120.degree. C.-150.degree. C. for 1 minute. The dip-and-dry
operation can be repeated one or more times when a higher thickness
is required. The coated substrates were then placed in an oven at
125.degree. C. for four hours.
Example 3
[0046] Preparation of a Substrate with a Polyamide Coating
Including Zinc
Example 3a
[0047] Preparation of A Polyamide with Side Chains
[0048] A polymer with side chains was prepared as detailed in
Example 1a.
Example 3b
Preparation of an Antimicrobial Polymer Solution from Example 3a
Polymer
[0049] A 2.5% solution of the polymer of Example 3a was prepared in
isopropanol. Then, 5 grams of zinc acetate were added to 50
milliliters of the 2.5% polymer solution. The solution was then
stirred until the zinc acetate completely dissolved. One milliliter
of triethylamine was then added to the solution under stirring. Two
milliliters of glutaraldehyde were then added to the solution. A
0.2 milliliter portion of tetrakis-(hydroxymethyl) phosphonium
chloride was then added to the solution followed by 0.3 milliliters
of dioctyl sebacate .
Example 3c
[0050] Preparation of a Substrate with an Antimicrobial Polymer
Coating
[0051] The polymer solution prepared in Example 3b was applied to a
10 millimeter by 10 millimeter polydimethylsiloxane substrate and a
10 millimeter by 10 millimeter polypropylene substrate. In doing
so, the substrates were dipped into the solution and removed after
0.5 to 2 minutes. Each wet substrate was dried and cured by hot air
at 120.degree. C.-150.degree. C. for 1 minute. The dip-and-dry
operation can be repeated one or more times when a higher thickness
is required. The coated substrates were then placed in an oven at
125.degree. C. for four hours.
Example 4
[0052] Preparation of a Substrate with a Polyamide Coating Base
Including Copper and A Polyamide Overcoat Including Silver
[0053] The polymer solution prepared in Example 2b was applied to a
10 millimeter by 10 millimeter polydimethylsiloxane substrate and a
10 millimeter by 10 millimeter polypropylene substrate forming the
copper base coat. In doing so, each substrate was dipped into the
solution and removed after 0.5 to 2 minutes. Each wet substrate was
dried and cured by hot air at 120.degree. C.-150.degree. C. for 1
minute. The polymer solution prepared in Example 1 b was then
applied to the coated polydimethylsiloxane substrate and the coated
polypropylene substrate forming the silver overcoat. In doing so,
each substrate was dipped into the solution and removed after 0.5
to 2 minutes. The coated substrates were then placed in an oven at
125.degree. C. for four hours. This produced polydimethylsiloxane
and polypropylene substrates having a polymer coating base
including copper and a polymer overcoat including silver.
Example 5
[0054] Preparation of a Substrate with a Polyamide Coating Base
Including Copper and A Polyamide Overcoat Including Zinc
[0055] The polymer solution prepared in Example 2b was applied to a
10 millimeter by 10 millimeter polydimethylsiloxane substrate and a
10 millimeter by 10 millimeter polypropylene substrate. In doing
so, each substrate was dipped into the solution and removed after
0.5 to 2 minutes. Each wet substrate was dried and cured by hot air
at 120.degree. C.-150.degree. C. for 1 minute. The polymer solution
prepared in Example 2b was then applied to the coated
polydimethylsiloxane substrate and the coated polypropylene
substrate. In doing so, each substrate was dipped into the solution
and removed after 0.5 to 2 minutes. The coated substrates were then
placed in an oven at 125.degree. C. for four hours. This produced
polydimethylsiloxane and polypropylene substrates having a polymer
coating base including copper and a polymer overcoat including
zinc.
Example 6
[0056] Preparation of a Substrate with a Polyamide Coating Base
Including Silver and A Polyamide Overcoat Including Copper
[0057] The polymer solution prepared in Example 1b was applied to a
10 millimeter by 10 millimeter polydimethylsiloxane substrate and a
10 millimeter by 10 millimeter polypropylene substrate. In doing
so, each substrate was dipped into the solution and removed after
0.5 to 2 minutes. Each wet substrate was dried and cured by hot air
at 120.degree. C.-150.degree. C. for 1 minute. The polymer solution
prepared in Example 2b was applied to the coated
polydimethylsiloxane substrate and the coated polypropylene
substrate. In doing so, each substrate was dipped into the solution
and removed after 0.5 to 2 minutes. The coated substrates were then
placed in an oven at 125.degree. C. for four hours. This produced
polydimethylsiloxane and polypropylene substrates having a polymer
coating base including silver and a polymer overcoat including
copper.
Example 7
[0058] Antimicrobial Activity Assay
[0059] The selection of target microorganisms for examining the
antimicrobial activity of the coated polydimethylsiloxane
substrates and the coated polypropylene substrates produced in the
Comparative Example and Examples 1c, 2c, 3c, 4, 5 and 6 was based
on the potential human pathogenic microorganisms, which include
gram positive bacteria, Bacillus subtilis and Staphylococcus
aureus; gram negative bacteria, E. coli and Pseudomonas aeruginosa;
and yeast, Candida albicans. Broth cultures were prepared for each
microorganism. Bacteria, Bacillus subtilis, Staphylococcus aureus,
E. coli and Pseudomonas aeruginosa were grown in 50 milliliters of
sterile tryptic soy broth in 500 milliliter baffle flask at 200
rpm. The cultures were grown at 37.degree. C. overnight, and used
for antimicrobial activity assay plates and stock culture. The
yeast, Candida albicans was cultivated in 50 milliliters of sterile
yeast malt broth in 250 milliliter baffle flask at 25-28.degree. C.
for 1 day and used for the activity assay plates and stock
culture.
[0060] Antimicrobial activity assay plates were then prepared.
Yeast malt agar and tryptic soy agar were autoclaved for 20
minutes. The sterile molten agar was allowed to cool to
42-45.degree. C. The prepared broth cultures of the target
microorganisms were inoculated to a final concentration of 5%
(v/v). The broth cultures were mixed to obtain a homogeneous
suspension, and a 20 milliliter aliquot of culture mixed agar media
was poured into sterile plastic petri dishes. The agar was allowed
to solidify, and dishes not to be used immediately were stored at
4.degree. C.
[0061] The coated polydimethylsiloxane substrates and the coated
polypropylene substrates produced in the Comparative Example and
Examples 1c, 2c, 3c, 4, 5 and 6 were placed on the prepared agar
plates. After incubation at 30.degree. C. for C. albicans and
37.degree. C. for the other microorganisms, respectively for 1-2
days, a clear zone of growth inhibition surrounding the coated
substrates was visible against a partially opaque background of
growth. The degree of inhibition was scored using the following
point system shown in Table 1. (When the inhibition zone was hazy,
the inhibition grade was ranked one lower degree.) The results are
shown in Table 2.
1TABLE 1 Score Score Description 0 No inhibition. 1/2 Inhibition,
but, not clearly measurable. 1 Clearly observable inhibition
wherein the diameter of the inhibition zone is in the range of
11-13 millimeters. 1 1/2 Half of a degree between 1 and 2. 2
Clearly observable inhibition wherein the diameter of the
inhibition zone is in the range of 14-16 millimeters. 3 Clearly
observable inhibition wherein the diameter of the inhibition zone
is in the range of 17-20 millimeters. 4 Clearly observable
inhibition wherein the diameter of the inhibition zone is over 21
millimeters.
[0062]
2TABLE 2 Test Example Staphylococcus Pseudomonas Candida Bacillus
No. Tested aureus aeruginosa albicans E. coli subtilis 1
Comparative 0 0 0 0 0 Example 2 Example 2c 1 1/2 1/2 1 2 3 Example
1c 1/2 0 1/2 0 3 4 Example 4 1 1/2 2 1 2 3 5 Example 3c 0 0 0 0 1 6
Example 5 1 1/2 1 1/2 1 1 2 7 Example 4 2 2 1 1/2 1 3 8 Example 6 0
1 1/2 0 1/2 9 Example 1c 0 1/2 1 0 1/2
Analysis
[0063] Upon review of the results for the inhibitory activity of
the coated polydimethylsiloxane substrates and the coated
polypropylene substrates produced in the Comparative Example and
Examples 1c, 2c, 3c, 4, 5 and 6 against bacterial/microbial growth
as shown in Table 2, many trends can be seen. Among the series of
antimicrobials tested, the coatings including two metals (i.e.,
galvanic coatings) demonstrated the highest activity, both in the
ability to suppress the colonization and its promising spectrum of
action. The polymer coatings including a single metal also show
significant progress and offer the same advantages as the galvanic
coating. The single metal coatings show good activity; however, the
activity is less than that of the galvanic coatings.
[0064] It is believed that the mode of metal chelation is likely to
contribute significantly to the results of the bioassay. Ionic
interaction can offer higher concentrations of the active component
in the incubation media. Meanwhile, immobilization by entrapping
the antimicrobial(s) in the bulk polymer coating would be expected
to show a more durable time of action.
[0065] It has also been discovered that the approach of the present
invention in incorporating the metal into the polymer coating is
quite advantageous and unexpected. The polymer used in the coating
serves to strongly chelate the metal. Without intending to be bound
by theory, it is believed that the polymer structure can be viewed
as that of an amino analogue of a crown ether. The coatings formed
are more durable than vapor deposited films used in existing
commercial products and contain the antimicrobial agent throughout
the coating thereby providing a controlled release of the
antimicrobial agent for several weeks.
[0066] Therefore, it can be seen that this work has provided an
improved antimicrobial polymeric composition that may be easily
applied as a coating to a substrate to provide an article which has
excellent antimicrobial properties. The antimicrobial polymeric
composition has several coating applications including, without
limitation, medical devices, antifouling applications for aqueous
and marine environments, and corrosion control.
[0067] Although the present invention has been described in
considerable detail with reference to certain embodiments, one
skilled in the art will appreciate that the present invention can
be practiced by other than the described embodiments, which have
been presented for purposes of illustration and not of limitation.
Therefore, the scope of the appended claims should not be limited
to the description of the embodiments contained herein.
* * * * *