U.S. patent application number 13/665915 was filed with the patent office on 2013-07-18 for antimicrobial polymeric compositions.
The applicant listed for this patent is Souvik Chakrabarty, Asima Chakravorty, Olufemi O. Oyesanya, Kenneth J. Wynne, Wei Zhang. Invention is credited to Souvik Chakrabarty, Asima Chakravorty, Olufemi O. Oyesanya, Kenneth J. Wynne, Wei Zhang.
Application Number | 20130183262 13/665915 |
Document ID | / |
Family ID | 48780111 |
Filed Date | 2013-07-18 |
United States Patent
Application |
20130183262 |
Kind Code |
A1 |
Wynne; Kenneth J. ; et
al. |
July 18, 2013 |
ANTIMICROBIAL POLYMERIC COMPOSITIONS
Abstract
A compound having the formula: ##STR00001## wherein n, y,
R.sub.1 and R.sub.2 are defined herein, and others, methods of
making of and using, and compositions made thereby which have an
antimicrobial resistance effect are described.
Inventors: |
Wynne; Kenneth J.;
(Midlothian, VA) ; Chakrabarty; Souvik; (Ithaca,
NY) ; Zhang; Wei; (Midlothian, VA) ;
Chakravorty; Asima; (Richmond, VA) ; Oyesanya;
Olufemi O.; (Chesapeake, VA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Wynne; Kenneth J.
Chakrabarty; Souvik
Zhang; Wei
Chakravorty; Asima
Oyesanya; Olufemi O. |
Midlothian
Ithaca
Midlothian
Richmond
Chesapeake |
VA
NY
VA
VA
VA |
US
US
US
US
US |
|
|
Family ID: |
48780111 |
Appl. No.: |
13/665915 |
Filed: |
October 31, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61552454 |
Oct 27, 2011 |
|
|
|
61552452 |
Oct 27, 2011 |
|
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Current U.S.
Class: |
424/78.3 ;
525/410; 528/402; 556/413 |
Current CPC
Class: |
C08G 18/6674 20130101;
C07F 7/1804 20130101; C08G 18/61 20130101; C08G 18/758 20130101;
C08G 65/18 20130101; C08G 18/4862 20130101; C08G 65/22 20130101;
C08G 2650/04 20130101; C08G 2650/64 20130101; A01N 55/00 20130101;
C09D 175/04 20130101; C08G 18/5066 20130101; C08G 2650/38 20130101;
C08G 65/226 20130101; C08G 18/718 20130101; C08G 2650/48 20130101;
C08G 2650/50 20130101; C08G 65/336 20130101 |
Class at
Publication: |
424/78.3 ;
528/402; 525/410; 556/413 |
International
Class: |
A01N 55/00 20060101
A01N055/00; C07F 7/18 20060101 C07F007/18; C08G 65/336 20060101
C08G065/336; C08G 65/22 20060101 C08G065/22; C08G 18/50 20060101
C08G018/50 |
Goverment Interests
GOVERNMENT LICENSE RIGHTS
[0002] This invention was made with government support under DMR
grants DMR-0207560 DMR-0802452, and DMR-1206259 awarded by the
National Science Foundation and Office of Naval Research Grant
#000140-81-09-2-2 awarded by the Office of Naval Research. The
government has certain rights in the invention. National Science
Foundation (DMR-- grants DMR-0207560, DMR-0802452, and
DMR-1206259), the Office of Naval Research (Grant
#000140-81-09-2-2) and the VCU School of Engineering Foundation
supported this research.
Claims
1. A compound having the formula: ##STR00046## wherein n is 0 to 1;
wherein y is an integer of 1-1000; and wherein R.sub.1 and R.sub.2
are not identical and are each independently --OCH.sub.2CF.sub.2H,
--OCH.sub.2CF.sub.2CF.sub.2H, --OCH.sub.2CF.sub.2CF.sub.2CF.sub.2H,
--Br, --(OC.sub.2H.sub.4).sub.x--O--CH.sub.3, wherein x is 0-11,
alkoxy, fluoroalkoxy, alkoxycycloalkyl, or a group having one of
the following formulas: ##STR00047## wherein a is 5-15; wherein b
is 0-5 wherein X is Cl, Br, I, OH, or NO.sub.3; and wherein A is
--CO.sub.2 or --SO.sub.3.
2. The compound of claim 1, having one of the following formulas:
##STR00048##
3. A polymer, comprising a polymerization product of: (A) the
compound of claim 1; (B) one or more of an isocyanate,
diisocyanate, or combination thereof; (C) optionally, a diol or
diamine chain extender; and (D) optionally, a diol selected from
the group polydimethylsiloxane diol, polytetramethylene oxide diol,
polypropylene oxide diol, polyethylene oxide diol, polybutadiene
diol, polyisobutylene diol, perfluorinated diol or a combination of
two or more thereof.
4. A method, comprising: reacting the compound of claim 1 with one
or more isocyanates having the formula: ##STR00049## to produce a
compound having the formula: formula: ##STR00050## wherein n is 0
to 1; wherein y is an integer of 1-1000; and wherein R.sub.1 and
R.sub.2 are not identical and are each independently
--OCH.sub.2CF.sub.2H, --OCH.sub.2CF.sub.2CF.sub.2H,
--OCH.sub.2CF.sub.2CF.sub.2CF.sub.2H, --Br,
--(OC.sub.2H.sub.4).sub.x--O--CH.sub.3, wherein x is 0-11, alkoxy,
fluoroalkoxy, alkoxycycloalkyl, or a group having one of the
following formulas: ##STR00051## wherein a is 5-15; wherein b is
0-5 wherein X is Cl, Br, I, OH, or NO.sub.3; and wherein A is
--CO.sub.2 or --SO.sub.3.
5. A compound having the formula: ##STR00052## wherein n is 0 to 1;
wherein y is an integer of 1-1000; and wherein R.sub.1 and R.sub.2
are not identical and are each independently --OCH.sub.2CF.sub.2H,
--OCH.sub.2CF.sub.2CF.sub.2H, --OCH.sub.2CF.sub.2CF.sub.2CF.sub.2H,
--Br, --(OC.sub.2H.sub.4).sub.x--O--CH.sub.3, wherein x is 0-11,
alkoxy, fluoroalkoxy, alkoxycycloalkyl, or a group having one of
the following formulas: ##STR00053## wherein a is 5-15; wherein b
is 0-5 wherein X is Cl, Br, I, OH, or NO.sub.3; and wherein A is
--CO.sub.2 or --SO.sub.3.
6. The compound of claim 5, having one of the following formulas:
##STR00054##
7. A composition, comprising a polymerization product of: (A) the
compound of claim 5; (B) one or more bis(trialkoxysilyl)alkanes
having the formula: ##STR00055## wherein R.sub.D is --CH.sub.3,
--CH.sub.2CH.sub.3, --CH.sub.2CH.sub.2CH.sub.3, or
--CH.sub.2CH.sub.2CH.sub.2CH.sub.3; and wherein r is an integer of
1-10; or one or more polydialkoxysiloxanes having the formula:
##STR00056## where R is --CH.sub.3 or --C.sub.2H.sub.5; (C) one or
more of an isocyanate, diisocyanate, or combination thereof; (D)
optionally, a diol or diamine chain extender; and (E) optionally, a
soft block diol selected from the group consisting of
polydimethylsiloxane diol, polytetramethylene oxide diol,
polypropylene oxide diol, polyethylene oxide diol, or a combination
of two or more thereof.
8. The composition of claim 7, wherein (B) is a
bis(trialkoxysilyl)alkane having the formula: ##STR00057##
9. A composition, comprising: (a) a reaction product of: (A) the
compound of claim 5; and (B) one or more bis(trialkoxysilyl)alkanes
having the formula: ##STR00058## wherein R.sub.D is --CH.sub.3,
--CH.sub.2CH.sub.3, --CH.sub.2CH.sub.2CH.sub.3, or
--CH.sub.2CH.sub.2CH.sub.2CH.sub.3; and wherein r is an integer of
1-10; or one or more polydialkoxysiloxanes having the formula:
##STR00059## where R is --CH.sub.3 or --C.sub.2H.sub.5; and (b) a
polymerization product of: (C) one or more of an isocyanate,
diisocyanate, or combination thereof; (D) optionally, a diol or
diamine chain extender; and (E) optionally, a soft block diol
selected from the group consisting of polydimethylsiloxane diol,
polytetramethylene oxide diol, polypropylene oxide diol,
polyethylene oxide diol, polydimethylsiloxane dipropylamine, or a
combination of two or more thereof.
10. The composition of claim 9, which is a blend of (a) and
(b).
11. A compound having the formula: ##STR00060## wherein R.sup.1,
R.sup.2, R.sup.3, R.sup.6, R.sup.7, R.sup.8 are each independently
hydrogen, alkyl, alkenyl, cycloalkyl, or aryl; wherein each R.sup.4
is independently a --CR.sup.9R.sup.10-- group wherein R.sup.9 and
R.sup.10 are each independently hydrogen or alkyl; wherein each
R.sup.5 is independently a --CR.sup.9R.sup.10-- group wherein
R.sup.9 and R.sup.10 are each independently hydrogen or alkyl;
wherein X is anion, Cl, Br, I, OH, or NO.sub.3; wherein n is 1-20;
and wherein m is 1-20.
12. The compound of claim 11, having the formula: ##STR00061##
13. A method of making the compound of claim 11, comprising
reacting a compound having the formula: ##STR00062## with a
compound having the formula: ##STR00063## to produce the compound
of claim 11.
14. The method according to claim 13, wherein the compounds have
the respective following formulas: ##STR00064##
15. A polymer, comprising a polymerization product of: (A) the
compound of claim 11; (B) a soft block diol selected from the group
polydimethylsiloxane diol, polytetramethylene oxide diol,
polypropylene oxide diol, polyethylene oxide diol, polybutadiene
diol, polyisobutylene diol, perfluorinated diol, or a combination
of two or more thereof; and (C) optionally, one or more
bis(trialkoxysilyl)alkanes having the formula: ##STR00065## wherein
R.sub.D is --CH.sub.3, --CH.sub.2CH.sub.3,
--CH.sub.2CH.sub.2CH.sub.3, or --CH.sub.2CH.sub.2CH.sub.2CH.sub.3;
and wherein r is an integer of 1-10; or one or more
polydialkoxysiloxanes having the formula: ##STR00066## where R is
--CH.sub.3 or --C.sub.2H.sub.5.
16. The polymer of claim 15, wherein: (A) is a compound having the
formula: ##STR00067## (B) is a polydimethylsiloxane diol; and (C)
is a compound having the formula: ##STR00068##
17. A polymer, comprising a polymerization product of: (A) a
compound having one of the following formulas: ##STR00069## wherein
k is 1-4; and A is --CO.sub.2 or --SO.sub.3; (B) a soft block diol
selected from the group polydimethylsiloxane diol,
polytetramethylene oxide diol, polypropylene oxide diol,
polyethylene oxide diol, polybutadiene diol, polyisobutylene diol,
perfluorinated diol, or a combination of two or more thereof; and
(C) optionally, one or more bis(trialkoxysilyl)alkanes having the
formula: ##STR00070## wherein R.sub.D is --CH.sub.3,
--CH.sub.2CH.sub.3, --CH.sub.2CH.sub.2CH.sub.3, or
--CH.sub.2CH.sub.2CH.sub.2CH.sub.3; and wherein r is an integer of
1-10; or one or more polydialkoxysiloxanes having the formula:
##STR00071## where R is --CH.sub.3 or --C.sub.2H.sub.5.
18. The polymer of claim 17, wherein: (B) is a polydimethylsiloxane
diol; and (C) is a compound having the formula: ##STR00072##
19. A method, comprising: contacting: (a) at least one selected
from the group consisting of polyurethane polymer, polyurethane
copolymer, or a combination thereof; and (b) at least one selected
from the group consisting of non-polar solvent, pentane,
cyclopentane, hexane, cyclohexane, benzene, toluene, 1,4-dioxane,
chloroform, diethyl ether, polar aprotic solvent, tetrahydrofuran,
dichloromethane, ethyl acetate, acetone, dimethylformamide,
acetonitrile, dimethyl sulfoxide, propylene carbonate, or a
combination thereof; and (c) at least one selected from the group
consisting of polar protic solvent, water, methanol, ethanol,
propanol, isopropanol, n-butanol, formic acid, or a combination
thereof; and thereafter separating, to produce a purified
polyurethane polymer, polyurethane copolymer, or a combination
thereof.
20. A method for making a polymer, comprising the method of claim
19.
21. A polymer, produced by the method of claim 19.
22. An article or device, comprising the polymer of claim 3 on a
surface thereof.
23. An article or device, comprising the composition of claim 7 on
a surface thereof.
24. An article or device, comprising the composition of claim 9 on
a surface thereof.
25. An article or device, comprising the polymer of claim 15 on a
surface thereof.
26. A method for killing a microbe, comprising contacting said
microbe with the polymer of claim 17.
27. A method for killing a microbe, comprising contacting said
microbe with the polymer of claim 3.
28. A method for killing a microbe, comprising contacting said
microbe with the composition of claim 7.
29. A method for killing a microbe, comprising contacting said
microbe with the composition of claim 9.
30. A method for killing a microbe, comprising contacting said
microbe with the polymer of claim 15.
31. A method for killing a microbe, comprising contacting said
microbe with the polymer of claim 17.
Description
REFERENCE TO EARLIER APPLICATIONS
[0001] This application claims priority to U.S. Provisional
Application Ser. Nos. 61/552,452, filed Oct. 27, 2011, and
61/552,454, filed Oct. 27, 2011.
FIELD OF THE APPLICATION
[0003] The present application relates to polymer compositions
which impart microbial resistance.
BACKGROUND
[0004] Infection acquired from health care environments is one of
the leading major medical complications in the present world.
Studies have shown that almost 6% of patients admitted to hospitals
acquire infections and the number of such cases is increasing.
According to reports by the US Center of Disease Control that
hospital acquired infections account for more than 2 million cases
leading to 99,000 deaths annually.
[0005] The most common hospital acquired infections include urinary
tract infections, surgical wound infections and those associated
with intravascular cannulas. The mode of transmission of these
infections is mostly by physical contact with infected medical
devices. Staphylococcus aureus, Pseudomonas aeruginosa, and
Escherichia coli are the most common bacterial isolates that give
rise to these infectious diseases. It has been observed that most
of the bacterial strains develop resistance to antibiotics over a
period of time. In the hospital environment, over 50% of
Staphylococcus aureus have developed resistance to methicillin,
which ultimately leads to surgical wound infection and catheter
related sepsis. Some of the emerging antibiotic resistant pathogens
include vancomycin resistant enterococci, vancomycin intermediate
staphylococcus, and multiple antibiotic resistant Gram negative
organisms like acinetobacter, enterobacter and mycobacterium.
[0006] Biocidal polymers offer promise in helping curb the spread
of infections by providing coatings for applications such as
biomedical devices or molded articles. An antimicrobial avoids
adhesion and proliferation of planktonic microbes on the surface by
either repelling or killing the microbes. While repelling surfaces
can be achieved by creating ultrahydrophobic surfaces, the killing
of microbes can be achieved by either biocide release or contact
kill. In some instances release and contact kill are combined.
Contact antimicrobial function is accomplished by covalently
bonding the biocide; thereby, promising durability. Because contact
kill precludes the biocide entering the bacterial metabolic
processes, elimination of bacterial resistance buildup may result.
Interest in contact kill has led to a number of studies on polymers
with covalently bound alkylammonium groups.
[0007] Contact kill silicone coatings include a class of biocidal
polysiloxanes with 3-(alkyldimethylammonium)propyl pendant groups.
Antimicrobial activity of PDMS chains terminated with quaternary
ammonium functionalities bearing oxyethylene moieties has been
studied. In a humid environment, these oxyethylene chains spread
out, exposing the ammonium moieties which imparts biocidal property
to these compounds. Simultaneously, cationic silicones have also
been used as surface modifiers, one of them being a reactive
silane,
(MeO).sub.3Si(CH.sub.2).sub.3N.sup.+Me.sub.2C.sub.18H.sub.37Cl.sup.-
(DC 5700). This compound, developed by Dow Corning, renders
bactericidal properties to surfaces like glass, cotton, polyester
fibers.
[0008] Quaternary function (sometimes referred to herein as "quat")
has been introduced into PDMS coatings using R.sub.quatSi(OR).sub.3
and condensation cure. With trifunctional R.sub.quatSi(OR).sub.3
competition must occur between quaternary function in the bulk
(crosslinker) and at the surface. Accordingly, 10-15 weight percent
R.sub.quatSi(OR).sub.3 was required to obtain modest antimicrobial
activity, which is undesirable due to expense.
[0009] Cationic surface active polyurethane surface modifiers as
antimicrobial coatings have been previously studied. Examples
include HMDI-BD based polyurethanes such as shown in FIG. 1 as the
polymer surface modifier containing a random P[AB] copolyoxetane
soft block, where A is a fluorine based oxetane (3FOx) and B
contains a quaternary ammonium side chain (C12) with a twelve
membered carbon chain. HMDI is H.sub.12MDI, (4,4'-(methylene
bis-(p-cyclohexyl isocyanate)) and BD is 1,4-butane diol have been
used for hard blocks in studies for antimicrobial coatings.
[0010] A small percentage of this modifier polyurethane was blended
with a HMDI-BD-PTMO polyurethane (base polyurethane) which is
commonly used in various industrial applications. It was observed
that the resulting P[AB] polyurethane, when blended with an
HMDI-BD-PTMO polyurethane, exhibited excellent antimicrobial
properties. However, the surface active charge was not stable, and
the antimicrobial property decreased drastically after two
weeks.
[0011] Betaines are a specialized family of zwitterion that
comprise both a cationic moiety and anionic functional groups.
Various betaines have shown good antibacterial activity and a broad
scope of inhibition. In previous studies, betaines were introduced
into to the polymer backbone through ether, amide, imide, or other
hydrolysable chemical bonds. However, these suffered from leaching
from the substrate and decreasing antibacterial activity during
use. The antibacterial agent siloxanesulfopropylbetaine (SSPB) with
a reactive alkoxysilane group for the finishing of cotton textiles
has been previously studied.
BRIEF DESCRIPTIONS OF THE FIGURES
[0012] FIG. 1 shows one embodiment of a conventional composition,
HMDI-BD(30)-P[(3FOx)(C12)-86:13-M.sub.n]
[0013] FIG. 2 presents biocidal tests described in the
examples.
[0014] FIG. 3 shows one embodiment of P[AB] copolyoxetane
polyurethane PSM; soft block "brush" surface concentration; and
base polyurethane.
[0015] FIG. 4 shows one embodiment of a conventional composition
PSM MDI/BD-P[(3FOx)(MEnOx)-p:(1-p)], 27-42 hard block wt %, and
base MDI/BD(36)-PTMO(2200).
[0016] FIG. 5 presents biocidal test results.
[0017] FIG. 6 presents one embodiment of an exemplary composition
and results observed therefor.
[0018] FIG. 7 presents zeta potential results described in the
examples.
[0019] FIG. 8 presents zeta potential results described in the
examples.
[0020] FIG. 9 presents antimicrobial results for an exemplary
composition.
[0021] FIG. 10 presents antimicrobial results for an exemplary
composition.
[0022] FIG. 11 presents one embodiment of end capping a diol.
[0023] FIG. 12 presents zeta potential results described in the
examples.
[0024] FIG. 13 presents one embodiment for preparation of the
quaternary ammonium modifier and a representative modified PDMS
coating.
[0025] FIG. 14 presents embodiments of condensation reactions.
[0026] FIG. 15 presents test results described in the examples.
[0027] FIG. 16 presents biocidal test results described in the
examples.
[0028] FIG. 17 presents test results described in the examples.
[0029] FIG. 18 presents test results described in the examples.
[0030] FIG. 19 presents biocidal test results described in the
examples.
[0031] FIG. 20 presents mechanical test results described in the
examples.
[0032] FIG. 21 presents one embodiment of a synthetic route of
DAPMDS-PDMS.
[0033] FIG. 22 presents one embodiment of a synthetic route of
DAPMDS-PDMS-PS.
[0034] FIG. 23 presents biocidal test results described in the
examples.
BRIEF SUMMARY OF THE SEVERAL EMBODIMENTS
[0035] One embodiment provides a polyoxetane diol having the
formula:
##STR00002## [0036] wherein n is 0 to 1; [0037] wherein y is an
integer of 1-1000; and [0038] wherein R.sub.1 and R.sub.2 are not
identical and are each independently --OCH.sub.2CF.sub.2H,
--OCH.sub.2CF.sub.2CF.sub.2H, --OCH.sub.2CF.sub.2CF.sub.2CF.sub.2H,
--Br, --(OC.sub.2H.sub.4).sub.x--O--CH.sub.3, wherein x is 0-11,
alkoxy, fluoroalkoxy, alkoxycycloalkyl, or a group having one of
the following formulas:
##STR00003##
[0039] wherein a is 5-15;
[0040] wherein b is 0-5
[0041] wherein X is Cl, Br, I, OH, or NO.sub.3; and
[0042] wherein A is --CO.sub.2 or --SO.sub.3.
[0043] In one embodiment, the polyoxetane diol may have one of the
following formulas:
##STR00004##
[0044] One embodiment provides a polymer, comprising a
polymerization product of: [0045] (A) the polyoxetane diol; [0046]
(B) one or more of an isocyanate, diisocyanate, or combination
thereof; [0047] (C) optionally, a diol or diamine chain extender;
and [0048] (D) optionally, a soft block diol selected from the
group polydimethylsiloxane diol, polytetramethylene oxide diol,
polypropylene oxide diol, polyethylene oxide diol, polybutadiene
diol, polyisobutylene diol, perfluorinated diol, or a combination
of two or more thereof.
[0049] In one embodiment, the isocyanate may have the formula:
##STR00005##
[0050] so that a compound having the following formula is
produced:
##STR00006## [0051] wherein n is 0 to 1; [0052] wherein y is an
integer of 1-1000; and [0053] wherein R.sub.1 and R.sub.2 are not
identical and are each independently --OCH.sub.2CF.sub.2H,
--OCH.sub.2CF.sub.2CF.sub.2H, --OCH.sub.2CF.sub.2CF.sub.2CF.sub.2H,
--Br, --(OC.sub.2H.sub.4).sub.x--O--CH.sub.3, wherein x is 0-11,
alkoxy, fluoroalkoxy, alkoxycycloalkyl, or a group having one of
the following formulas:
##STR00007##
[0054] wherein a is 5-15;
[0055] wherein b is 0-5
[0056] wherein X is Cl, Br, I, OH, or NO.sub.3; and
[0057] wherein A is --CO.sub.2 or --SO.sub.3.
[0058] One embodiment provides an end-capped compound having the
formula:
##STR00008## [0059] wherein n is 0 to 1; [0060] wherein y is an
integer of 1-1000; and [0061] wherein R.sub.1 and R.sub.2 are not
identical and are each independently --OCH.sub.2CF.sub.2H,
--OCH.sub.2CF.sub.2CF.sub.2H, --OCH.sub.2CF.sub.2CF.sub.2CF.sub.2H,
--Br, --(OC.sub.2H.sub.4).sub.x--O--CH.sub.3, wherein x is 0-11,
alkoxy, fluoroalkoxy, alkoxycycloalkyl, or a group having one of
the following formulas:
##STR00009##
[0062] wherein a is 5-15;
[0063] wherein b is 0-5
[0064] wherein X is Cl, Br, I, OH, or NO.sub.3; and
[0065] wherein A is --CO.sub.2 or --SO.sub.3.
[0066] In one embodiment, the end-capped compound may have one of
the following formulas:
##STR00010##
[0067] One embodiment provides a composition, comprising a
polymerization product of: [0068] (A) the end-capped compound;
[0069] (B) one or more bis(trialkoxysilyl)alkanes having the
formula:
[0069] ##STR00011## [0070] wherein R.sub.D is --CH.sub.3,
--CH.sub.2CH.sub.3, --CH.sub.2CH.sub.2CH.sub.3, or
--CH.sub.2CH.sub.2CH.sub.2CH.sub.3; and wherein r is an integer of
1-10;
[0071] or one or more polydialkoxysiloxanes having the formula:
##STR00012## [0072] where R is --CH.sub.3 or --C.sub.2H.sub.5;
[0073] (C) one or more of an isocyanate, diisocyanate, or
combination thereof; [0074] (D) optionally, a diol or diamine chain
extender; and [0075] (E) optionally, a soft block diol selected
from the group consisting of polydimethylsiloxane diol,
polytetramethylene oxide diol, polypropylene oxide diol,
polyethylene oxide diol, or a combination of two or more
thereof.
[0076] In one embodiment, (B) may have the formula:
##STR00013##
[0077] One embodiment provides a composition, comprising: [0078]
(a) a reaction product of: [0079] (A) the end-capped compound; and
[0080] (B) one or more bis(trialkoxysilyl)alkanes having the
formula:
[0080] ##STR00014## [0081] wherein R.sub.D is --CH.sub.3,
--CH.sub.2CH.sub.3, --CH.sub.2CH.sub.2CH.sub.3, or
--CH.sub.2CH.sub.2CH.sub.2CH.sub.3; and wherein r is an integer of
1-10;
[0082] or one or more polydialkoxysiloxanes having the formula:
##STR00015## [0083] where R is --CH.sub.3 or --C.sub.2H.sub.5;
[0084] and [0085] (b) a polymerization product of: [0086] (C) one
or more of an isocyanate, diisocyanate, or combination thereof;
[0087] (D) optionally, a diol or diamine chain extender; and [0088]
(E) optionally, a soft block diol selected from the group
consisting of polydimethylsiloxane diol, polytetramethylene oxide
diol, polypropylene oxide diol, polyethylene oxide diol,
polydimethylsiloxane dipropylamine, or a combination of two or more
thereof.
[0089] The composition may be either a blend, copolymer, or
crosslinked copolymer matrix. In one embodiment, the composition is
a blend of (a) and (b).
[0090] One embodiment provides a difunctional surface modifying
agent, having the formula:
##STR00016## [0091] wherein R.sup.1, R.sup.2, R.sup.3, R.sup.6,
R.sup.7, R.sup.8 are each independently hydrogen, alkyl, alkenyl,
cycloalkyl, or aryl; [0092] wherein each R.sup.4 is independently a
--CR.sup.9R.sup.10-- group wherein R.sup.9 and R.sup.10 are each
independently hydrogen or alkyl; [0093] wherein each R.sup.5 is
independently a --CR.sup.9R.sup.10-- group wherein R.sup.9 and
R.sup.10 are each independently hydrogen or alkyl; [0094] wherein X
is anion, Cl, Br, I, OH, or NO.sub.3; [0095] wherein n is 1-20; and
[0096] wherein m is 1-20.
[0097] In one embodiment, the difunctional surface modifying agent
has the formula:
##STR00017##
[0098] One embodiment provides a method of making the difunctional
surface modifying agent, comprising reacting a compound having the
formula:
##STR00018##
[0099] with a compound having the formula:
##STR00019##
[0100] to produce the surface modifying agent.
[0101] In one embodiment, the reactants for the surface modifying
agent have the respective following formulas:
##STR00020##
[0102] One embodiment provides a polymer, comprising a
polymerization product of: [0103] (A) the difunctional surface
modifying agent; [0104] (B) a soft block diol selected from the
group polydimethylsiloxane diol, polytetramethylene oxide diol,
polypropylene oxide diol, polyethylene oxide diol, polybutadiene
diol, polyisobutylene diol, perfluorinated diol, or a combination
of two or more thereof; and [0105] (C) optionally, one or more
bis(trialkoxysilyl)alkanes having the formula:
[0105] ##STR00021## [0106] wherein R.sub.D is --CH.sub.3,
--CH.sub.2CH.sub.3, --CH.sub.2CH.sub.2CH.sub.3, or
--CH.sub.2CH.sub.2CH.sub.2CH.sub.3; and
[0107] wherein r is an integer of 1-10;
[0108] or one or more polydialkoxysiloxanes having the formula:
##STR00022## [0109] where R is --CH.sub.3 or --C.sub.2H.sub.5.
[0110] In one embodiment, (A) is a compound having the formula:
##STR00023## [0111] (B) is a polydimethylsiloxane diol; and [0112]
(C) is a compound having the formula:
##STR00024##
[0113] One embodiment provides a polymer, comprising a
polymerization product of: [0114] (A) a compound having one of the
following formulas:
[0114] ##STR00025## [0115] wherein k is 1-4; [0116] and wherein A
is --CO.sub.2 or --SO.sub.3; [0117] (B) a soft block diol selected
from the group polydimethylsiloxane diol, polytetramethylene oxide
diol, polypropylene oxide diol, polyethylene oxide diol,
polybutadiene diol, polyisobutylene diol, perfluorinated diol, or a
combination of two or more thereof; and [0118] (C) optionally, one
or more bis(trialkoxysilyl)alkanes having the formula:
[0118] ##STR00026## [0119] wherein R.sub.D is --CH.sub.3,
--CH.sub.2CH.sub.3, --CH.sub.2CH.sub.2CH.sub.3, or
--CH.sub.2CH.sub.2CH.sub.2CH.sub.3; and
[0120] wherein r is an integer of 1-10;
[0121] or one or more polydialkoxysiloxanes having the formula:
##STR00027##
[0122] where R is --CH.sub.3 or --C.sub.2H.sub.5.
[0123] In one embodiment in the polymer above, (B) is a
polydimethylsiloxane diol; and [0124] (C) is a compound having the
formula:
##STR00028##
[0125] The ranges described in the embodiments above can have any
values or subranges therebetween. For example, wherein n is 0 to 1,
referring to a mixture, n can have any value therebetween,
including 0, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09,
0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, any combination
thereof, or any subrange therein. This nomenclature and equivalent
versions of it are well-known in the polymer arts.
[0126] For example, wherein y is an integer of 1-1000, y may adopt
any value including for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20,
30, 40, 50, 60, 70, 80, 90, 100, 200, 250, 500, 750, 900, 1000, any
combination thereof, or any subrange therein. This nomenclature and
equivalent versions of it are well-known in the polymer arts.
[0127] So long as R.sub.1 and R.sub.2 are not identical, each may
be independently --OCH.sub.2CF.sub.2H,
--OCH.sub.2CF.sub.2CF.sub.2H, --OCH.sub.2CF.sub.2CF.sub.2CF.sub.2H,
--Br, --(OC.sub.2H.sub.4).sub.x--O--CH.sub.3 (wherein x is 0-11,
including 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 or any subrange
therein), alkoxy, fluoroalkoxy, alkoxycycloalkyl, or a group having
one of the following formulas:
##STR00029##
[0128] In the formulas described, a is 5-15 or any subrange
therebetween, including 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or
any subrange therein.
[0129] In the formulas described, b is 0-5 or any subrange
therebetween, including 0, 1, 2, 3, 4, 5, or any subrange
therein.
[0130] In the formulas described, r is an integer of 1-10 or any
subrange therebetween, including 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or
any subrange therein.
[0131] In the formulas described, X may be any one of Cl, Br, I,
OH, or NO.sub.3 or, if more than one compound is present, each
compound may have a different X, or every compound may have the
same X.
[0132] In the formulas described, A is --CO.sub.2 or --SO.sub.3 or,
if more than one compound is present, each compound may have a
different A or every compound may have the same A.
[0133] In the formulas described, the isocyanates and diisocyanates
are not particularly limited and, given the teachings herein
combined with the knowledge of one of ordinary skill, they can be
selected as appropriate. For example, methylene dicyclohexyl
diisocyanate, diphenylmethane diisocyanate, hexamethylene
diisocyanate, isophorone diisocyanate, toluene diisocyanate,
xylylene diisocyanate, cyclohexane diisocyanate, tetramethyl
xylylene diisocyanate, trimethylhexamethylene diisocyanate,
norbornane diisocyanate, phenylene diisocyanate, or a combination
of two or more thereof.
[0134] Similarly, the isocyanate is not particularly limiting.
Non-limiting examples of the isocyanate include compounds having
the formula:
##STR00030##
[0135] wherein R.sub.D is --CH.sub.3, --CH.sub.2CH.sub.3,
--CH.sub.2CH.sub.2CH.sub.3, --CH.sub.2CH.sub.2CH.sub.2CH.sub.3, and
p is an integer of 1-10. The p range includes all values and
subranges therebetween, including 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,
and 11, or any subrange therein. In one embodiment, p is 1, 2, 3,
or 4.
[0136] If desired, one or more chain extenders may be used, which
are not particularly limiting. Any suitable diol or diamine chain
extender may be used. Non-limiting examples of the diol include a
C.sub.1-10 alkylene diol, C.sub.1-10 alkenylene diol, C.sub.1-20
aralkylene diol, 1,4-butanediol, or the like, or combinations of
two or more thereof, though others are possible. Similarly,
non-limiting examples of diamine chain extenders include C.sub.1-10
alkylene diamine, C.sub.1-10 alkenylene diamine, C.sub.1-20
aralkylene diamine, or the like or combinations of two or more
thereof, though others are possible.
[0137] Similarly, in the formulas described, the diol or diamine
chain extender are not particularly limited and, given the
teachings herein combined with the knowledge of one of ordinary
skill, they can be selected as appropriate. For example, chain
extending diols may include a C.sub.1-10 alkylene diol, C.sub.1-10
alkenylene diol, C.sub.1-20 aralkylene diol, 1,4-butanediol, or the
like, or combinations of two or more thereof, although others are
possible. Similarly, non-limiting examples of diamine chain
extenders include C.sub.1-10 alkylene diamine, C.sub.1-10
alkenylene diamine, C.sub.1-20 aralkylene diamine, or the like, or
combinations of two or more thereof, although others are
possible.
[0138] Similarly, in the formulas described, the soft block diol
may be suitably chosen from known polydimethylsiloxane diols,
polytetramethylene oxide diols, polypropylene oxide diols,
polyethylene oxide diols, polybutadiene diols, polyisobutylene
diols, perfluorinated diols, or a combination of two or more
thereof.
[0139] HMDI/BD(30)-[(4FOx)(C12)] has the following structure:
##STR00031##
[0140] In one embodiment, a hybrid modifier may be desirable in
view of stability. In another embodiment, the
HMDI/BD(30)-[(4FOx)(C12)] polyurethane modifier exhibits a
remarkable improvement over the conventional "--CF.sub.3"
copolyoxetane in view of the higher C12 (34 mole percent,
p=66).
[0141] In one embodiment, the molecular weight for the
P[(4FOx)(C12)] is 5.7 kDa, which may suitably be determined by end
group MW (.sup.1H-NMR).
[0142] In one embodiment, the polyurethane modifier is
HMDI/BD(30)-[(ME2Ox)(C12)], which may be desirable in view of
biocompatibility and/or cytocompatibility.
[0143] In one embodiment, the polyurethane modifier is
HMDI/BD(30)-[(ME2Ox)(C12)] (with 14 mol % C12).
[0144] In one embodiment, a hybrid modifier has the following
formula:
##STR00032##
[0145] In one embodiment, for above hybrid modifier, p can range
from 20-80 mol % or any subrange therein. In one embodiment, p is
50 mol % but the range.
[0146] In the compounds and compositions described, using
HMDI/BD(XX)-P[(4FOx)(C12)-YY:ZZ-molecular weight] as a generic
example, the "XX", "YY", and "ZZ" have the following meanings. XX
is the weight percent of the "hard block" component (in this
example, an HMDI/BD polyurethane, and YY is the weight percent soft
block (which, in this example, is P(4FOx)(C12) copolyoxetane). The
corresponding weight percent of the soft block copolyoxetane is
understood, wherein the weight percents of the hard block and soft
block total to 100%. The weight percents are based on those of the
starting materials.
[0147] For convenience, one embodiment of a representative P[AB]
diol is shown below:
##STR00033##
[0148] In the soft block described above (in this example, the
P(4FOx)(C12) copolyoxetane) but more generically, "P[AB], the YY:ZZ
refer to the mole percents of the respective A and B components (in
this example, A is 4FOx oxetane co-monomer (YY), and B is the
quaternised surface active oxetane co-monomer "C 12".
[0149] The "-molecular weight" notation is that of the starting
P[AB] diol.
[0150] In the polymer modifiers compounds and compositions
described herein, XX may is not particularly limited and may
suitably range from 20-40, which includes all values and subranges
therebetween, including 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,
31, 32, 33, 34, 35, 376, 37, 38, 39, 40 wt. %, or any subrange
therein. From this, the corresponding weight percent of soft block
(which is not particularly limited and may range from 60-80) may be
easily calculated.
[0151] The YY mole percent is not particularly limited and may
suitably range from 20-80, which range includes all values and
subranges therebetween, including 20, 21, 22, 23, 24, 25, 26, 27,
28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 50, 60, 70, 80
mol %, or any subrange therein. Similarly, the ZZ mole percent may
range from 80-20 mol % and may be easily calculated.
[0152] The molecular weight of the starting P[AB] diol is not
particularly limited and may suitably range from 200-10,000 Da,
which range includes all values and subranges therebetween,
including 200, 205, 225, 250, 275, 500, 505, 510, 515, 525, 550,
575, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1100, 1150,
1250, 1500, 2000, 2500, 5000, 7500, and 10,000 Da, or any subrange
therein.
[0153] In one embodiment, wherein P[(4FOx)(C12)] is used as the
diol, YY:ZZ is 66:34.
[0154] In one embodiment, wherein P[(ME2Ox)(C12)] is used as the
diol, YY:ZZ is 50:50.
[0155] In one embodiment, wherein P[(ME2Ox)(C12)] is used as the
diol, the molecular weight may be 2500 Da.
[0156] In one embodiment, a hybrid modification may be used, in
which a triethoxysilyl isocyanate is used to end-cap the diol,
which is then combined with an alkoxysilane "booster" for the
siliceous domain, added to base polyurethane solution, and drip
coated or cast.
[0157] In one embodiment, amount of difunctional quaternized or
zwitterionic surface modifying agent present in the modified PDMS
is not particularly limited, and may be suitably range from 0.01 to
25 wt. %. This range includes all values and subranges
therebetween, including 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07,
0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 wt. %, or any subrange
therein.
[0158] In one embodiment, the amount of bis(trialkoxysilyl)alkane
or poly(dialkoxysiloxane) added to the compositions is not
particularly limited, and may suitably range from 0 to 35 wt. %.
This range includes all values and subranges therebetween,
including 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09,
0.1, 0.2, 0.3, 0.4, 0.5, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6,
7, 8, 9, 10, 15, 20, 25, 30, 35 wt. %, or any subrange therein. One
or more than one bis(trialkoxysilyl)alkane or
poly(dialkoxysiloxane) may be used. Combinations of
bis(trialkoxysilyl)alkane and poly(dialkoxysiloxane) may also be
used. Typically, these can be used to "boost" the weight fraction
of the siliceous component in the surface modifier. Such
poly(dialkoxysiloxanes) are well known and may be obtained from
Gelest PSI-021, Gelest PSI-023, or PSI-026. The `n` subscript in
the poly(dialkoxysiloxane) can range from 1-1000, or any integer
therebetween, including 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25,
30, 50, 75, 100, 200, 250, 500, 750, or any subrange therein.
[0159] The compositions may be prepared and applied to a surface or
made into a device or article to impart antimicrobial resistance.
As such, one embodiment relates to a device or an article having an
antimicrobial surface. In one embodiment, the action is of the
contact kill type, wherein the antimicrobial component does not
leach out of the surface, device, or article. Non-limiting examples
of such articles or devices include surface coating or composition
suitable for painting, e.g., a paint, an adhesive, sealant, caulk,
tubing, catheter, urinary catheter, intubation tube, shunt,
cerebral shunt, transdermal device, surgical implant, artificial
joint implant, medical device, bandage, dressing, fabric, clothing,
utensil, food contacting surface, dental device, dental implant,
breathing device, mask, tracheal implant, cannula, intravascular
cannula, glove, suture material, thread, as sizing for textile
materials, and the like. The compounds and compositions described
herein may be used in combination as an additive, blend, copolymer,
or coating with any bulk polymer such as polyesters, polyacrylates,
polyurethenes, styrene butadiene rubbers, cellulosic, cotton, and
the like, or other surface such as glass.
[0160] In one embodiment, the antimicrobial resistance may be
effective against one or more of Staphylococcus aureus, Pseudomonas
aeruginosa, Escherichia coli, methicillin-resistant Staphylococcus
aureus, vancomycin resistant enterococci, vancomycin intermediate
staphylococcus, multiple antibiotic resistant Gram negative
organisms, acinetobacter, enterobacter, mycobacterium.
[0161] One embodiment provides a method, comprising contacting (a)
at least one selected from the group consisting of polyurethane
polymer, polyurethane copolymer, or a combination thereof; and (b)
a composition comprising tetrahydrofuran and at least one alcohol
selected from the group consisting of methanol, ethanol, propanol,
isopropanol, or a combination thereof; and thereafter separating,
to produce a purified polyurethane polymer, polyurethane copolymer,
or a combination thereof.
[0162] Any of the polymers, blends, hybrid compositions, base
polymers, coatings, and articles described herein can benefit from
the application of this method.
[0163] In one embodiment, the method for purifying is carried out
at a temperature of 25 to 100.degree. C. This range includes all
values and subranges therebetween, including 25, 30, 35, 40, 45,
50, 55, 60, 65, 70, 75, 80, 85, 90, 95, and 100.degree. C.
[0164] If desired, the method for purifying additionally and
optionally includes drying the purified polyurethane polymer,
polyurethane copolymer, or combination thereof.
[0165] The polyurethane polymer or copolymer is not particularly
limited, and the method for purifying may be suitably used on any
polyurethane moiety. For example, the polyurethane can be any of an
alternating copolymer, periodic copolymer, statistical copolymer,
random copolymer, block copolymer, diblock copolymer, triblock
copolymer, branched copolymer, linear copolymer, star copolymer,
brush copolymer, comb copolymer, crosslinked copolymer,
thermoplastic elastomeric copolymer, HMDI/BD-30-(PTMO), copolymer
of polyurethane and 4FOx-C12, copolymer of polyurethane and 3FOx,
copolymer of polyurethane and 3FOx-C12, Lubrizol ESTANE
ALR-E72A.TM. or a combination thereof.
[0166] The relative amounts of tetrahydrofuran and alcohol used in
the purification method are not particularly limiting. In one
embodiment, the THF and alcohol may have a weight:weight ratio
ranging from 90:10 to 10:90. This range includes all values and
subranges therebetween, including any of 90, 85, 80, 75, 70, 65,
60, 55, 50, 45, 40, 35, 30, 25, 20, 15, and 10 to any of 10, 15,
20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, and 90
(weight:weight).
[0167] The contacting time in the purification method is not
particularly limiting. In one embodiment, it may suitably range
from 0.1 hr to 400 hrs. This range includes all values and
subranges therebetween, including 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8,
9, 10, 12, 24, 36, 48, 60, 72, 96, 100, 120, 150, 180, 200, 300,
and 400 hrs or any combination thereof.
[0168] In one embodiment of the purification method, the alcohol is
aqueous.
[0169] So long as it is applied to a polyurethane moiety, the
purification method may be used as part of a polymerization method.
In one embodiment, the polymerization method comprises purifying
one or more of a reactant oligomer, prepolymer, combination
thereof, or the like as appropriate before further polymerizing. In
another embodiment, the purification method comprises purifying a
resultant polymer, copolymer, combination thereof, or the like as
appropriate. Combinations are possible.
[0170] One embodiment provides a purified polyurethane polymer,
copolymer, or combination thereof produced by the purification
method.
[0171] In the context of the method or products prepared thereby,
for a polymer to be `purified` it need not be completely or even
substantially purified after undergoing the method. That is, it may
still contain a measurable or even substantial portion of
impurities or contamination, e.g., unreacted monomers or reactants,
surface active molecules, small molecules, water-soluble
components, and the like. One way to determine whether contaminants
remain is so place the purified polymer into clean water for a few
minutes, then interrogate that water using a dynamic contact angle
(DCA) apparatus and a clean flamed glass slide. Such methods are
well-known in the art.
[0172] Conventional condensation cure is used to make coatings and
elastomers. An additive that copolymerizes with standard
polydimethylsiloxane diols and alkoxysilane crosslinking agents
concentrates at the surface of the coating or article and generates
contact antimicrobial function (no release of biocide). The
additive is selectively concentrated at the surface of the coating
or elastomeric object and is effective at a level of 1 wt %. The
additive confers highly effective contact kill of bacteria in tests
that mimic a cough, sneeze, or touch.
[0173] A recent study was done on poly(dimethylsiloxane) based
coatings containing quaternary ammonium salt (QAS 1) moieties,
exerting biocidal activity through contact kill A major point of
concern about this study was the use of a high weight percent
(10-15%) of the trimethoxy functionalized alkylammonium salt (QAS
1).
[0174] The moderate biocidal activity observed for these coatings
suggest the presence of a substantial amount of the alkylammonium
modifier QAS 1, in the bulk.
##STR00034##
[0175] We have developed a new strategy for surface modification of
PDMS with cationic moieties. We have found that the presence of a
dimethoxy functional group provides an unexpected improvement
compared to QAS 1. A difunctional alkoxy group allows incorporation
of the modifier in the linear polymer chain favoring surface
concentration, and prevents it from getting trapped in the bulk.
While not wishing to be limited by theory, it is believed that the
alkylammonium surface modifier being in the linear chain would have
greater mobility and a tendency of concentrating at the
surface.
##STR00035##
[0176] We have quantitatively generated a quaternary ammonium salt,
which is a difunctional quaternary alkoxide (referred to herein as
"SMA 1" or "QAM"), in a one-step reaction of the commercially
available chloropropyl precursor with C12 amine. Probing the
efficacy of SMA 1, 1 wt % was added to a 5 kDa PDMS diol followed
by conventional condensation cure with BTSE, 8. A bacterial spray
test with a 30 min exposure time gave >99% kill against Gram(-)
(P. aeruginosa, E. coli) and Gram(+) (S. aureus) bacteria. Results
indicate good stability in air over several months, which is
surprising.
[0177] One embodiment relates to the development of new silicone
antibacterial modifiers for applications such as coatings and
tubing used in biomedical applications. One embodiment relies on
surface concentration of betaines, a specialized family of
zwitterions, comprising of cationic moiety such as quaternary
ammonium species and anionic functional groups like sulfo-,
carboxy-, hydroxyl-, and phosphobetaines, and the approach is
introducing a group that is "self chaperoning" or self-surface
concentrating into the polydimethylsiloxane (PDMS) main chain. The
resulting coating or object has a contact antibacterial surface.
The modified resin is suitable for a wide variety of applications
including tubing, implants, breathing devices, masks, tracheal
implants, and the like.
[0178] It is known that with long fluorous side chains
(.gtoreq.C.sub.f8, C.sub.f=perfluorinated carbon), replacement of
terminal --CF.sub.3 by --CF.sub.2H results in decreased surface
tension. For fluoromethacrylate block copolymers having "short"
side chains (<C.sub.f8) a similar reduction of .theta..sub.adv
and .theta..sub.rec is observed by substituting --CF.sub.3
terminated side chains with --CF.sub.2H termination. We have found
that a co-repeat unit with a --CF.sub.2H side chain together with a
co-repeat unit having a quaternary side chain is more stable both
in dry and wet conditions and is less prone to surface phase
separation.
[0179] In one embodiment, we have found that the so-called, "4FOx"
(a fluorinated side chain with a --CF.sub.2H end group) instead of
3FOx, may be a more useful "chaperone" to direct the cationic
antimicrobial moiety to the surface because of its amphiphilic
nature.
[0180] In one embodiment, bacteria exposed to the contact kill
antimicrobial surfaces described herein do not build up resistance
to contact kill.
[0181] In one embodiment, the polydimethylsiloxane (PDMS) coatings
and antimicrobial surfaces described herein result in a contact
kill of bacteria without release of biocide.
[0182] Stepwise synthesis of surface modifying additive `SMA 1` and
its incorporation into PDMS elastomers.
##STR00036##
[0183] The surface modifying additive, SMA 1 is synthesized by
performing a substitution reaction between the 3-chloropropyl
dimethoxysilane 1 and N,N-dodecyldimethylamine 2, leading to
replacement of the chlorine atom in 1 by the tertiary aminie. This
substitution reaction incorporates a quaternary positive charge in
the modifier which can then be reacted in varying weight percents
with a PDMS elastomer. It is believed that the charge bearing
quaternary ammonium groups in SMA 1 may be entropically driven to
the surface producing coatings with near surface quaternised
cationic moieties.
[0184] In one embodiment, synthesis of the quaternised PDMS
compositions involves a two step method. The first step involves a
substitution reaction between 3-chloropropyl dimethoxysilane 1, and
N,N-dimethyldodecylamine 2. Step 2 involves a condensation reaction
between the precursor synthesized in step 1, a crosslinking agent 3
and a low molecular weight silanol terminated PDMS.
[0185] Precursor Synthesis.
[0186] In one embodiment, SMA 1 may be made by reacting 5 g (27.4
mmol) of the chlorosilane 1 with 5.5 g (25.8 mmol) of the
dodecylamine 2 in a reaction vessel at 30.degree. C. for 48 hrs. A
constant supply of nitrogen was maintained inside the reaction
flask to eliminate the presence of any moisture since the methoxy
functional groups present in 1 are susceptible to hydrolysis.
Chlorosilane 1 was taken in excess since its high volatility
enabled removal of traces of unreacted 1 under vacuum.
[0187] In one embodiment, a P-Q-C12 (a quaternised PDMS) synthesis
involves reacting various wt % of the SMA1 with a silanol
terminated PDMS (4 kDa), a crosslinking agent to promote the
formation of a network structure. This reaction is allowed to take
place in the presence of 0.5 wt % DBTDA catalyst.
[0188] In one embodiment, minuscule amount of SMA1 in the PDMS
matrix will surface concentrate and confer antimicrobial
characteristic to the polymer.
[0189] In one embodiment, the alkyl side chain bearing a cationic
charge may be entropically driven to the surface of the
polymer.
[0190] Assay for Antimicrobial Activity.
[0191] Bacterial strains of Pseudomonas aeruginosa PAO1 and
Staphylococcus aureus ATCC-25904 were used for investigating the
biocidal efficacy of PDMS doped with 0.5 wt % of SMA1. The
bacterial cultures were streaked on Luria Agar plates from frozen
stocks and incubated overnight at 37.degree. C. A single colony
from each strain was used to inoculate 6 ml of Luria Broth (LB),
was grown overnight at 37.degree. C. at 225 rpm. A starting
inoculum of 10.sup.8-10.sup.9 colony forming units per milliliter
(CFU/ml) of the desired pathogen was used for the culture. Aliquots
from the overnight culture were taken and reinoculated in a 1:100
dilution in LB.
[0192] A biocidal test was devised to simulate aerosol deposition
(cough, sneeze) of pathogenic bacteria. With a sprayer designed to
deliver a controlled volume, a challenge of Pseudomonas aeruginosa
(10.sup.7 CFU/mL) was delivered to the surface of these PDMS
coatings containing 0.5 wt % of SMA1. A constant volume of 5-mg of
the bacterial culture was sprayed on the coated microscope slides.
The coated slides were placed in a constant humidity (85-95%)
environment. A constant humidity is important for testing because
control experiments in ambient air showed irreproducible fractions
of dead bacteria as a function of time. After 30 min, the slides
were placed in saline solution and vortexed for 2 min. One hundred
microliter aliquots and dilutions were removed and spread onto agar
plates that were incubated at 37.degree. C. for 18 h. Live bacteria
(cfu's) on plates were counted to obtain the percent kill and log
reduction. A 30 minute residence time was chosen in order to
achieve complete kill. The same protocol was followed for
microscope slides coated with conventional condensation cured PDMS
that served as a control.
[0193] Antimicrobial Activity of the 0.5 wt % P-Q-C12
Composition.
[0194] Biocidal efficacy of the 0.5 wt % P-Q-C12 coatings have been
investigated against P. aeruginosa and S. aureus and the results
have been compared with the antimicrobial activity for a
conventional PDMS coated slide. One aim was also to investigate the
biocidal efficacy of this quaternised PDMS composition against both
Gram (+ve) S. aureus and Gram (-ve) P. aeruginosa bacteria. See
FIG. 2.
[0195] For S. aureus, the control slide had an average of 118 and
123 cfu, whereas the 0.5 wt % PQ-C12 slides had 30 and 46 cfu
respectively.
[0196] For P. aeruginosa, the PDMS control had 331 and 305 cfu of
viable bacteria, while the 0.5 wt % PQ-C12 coated slide had 66 and
87 colonies remaining. It was observed that this surface modifier
had an .about.69% kill for S. aureus and an .about.75% kill for P.
aeruginosa strains.
[0197] Investigation of Varying the Weight Percent of the PQ-C12
Modifier on Biocidal Activity.
[0198] We have achieved a considerable antimicrobial activity by
having 0.5 wt % of the modifier in the matrix. Varying the amounts
of the cationic surface modifier can be correlated to the biocidal
efficacy of the modified PDMS.
[0199] A 1 wt % and 2 wt % of the modifier in PDMS has been used in
biocidal tests to investigate their antimicrobial effectiveness.
These modified coatings were also tested against Escherecia coli, a
Gram (-ve) bacteria, in addition to the S. aureus and P.
aeruginosa.
[0200] Antimicrobial Activity of the 1 wt % and the 2 wt % P-Q-C12
Compositions.
[0201] An improvement in the antimicrobial activity of these
modified PDMS coatings were observed on increasing the amount of
surface modifier. A remarkable improvement in antimicrobial
effectiveness has been observed going from 0.5% to 1% of the PQ-C12
surface modifier. The percent kill for S. aureus increased from 69%
to 99.3%, similarly, 99.5 for P. aeruginosa. The 1% modified
coatings were also very effective against E. coli, affecting a
97.8% kill in the first 30 minutes.
[0202] Results with the 2% modified PDMS coating has been achieved.
It has been observed that the 2% modified coating affects a 98.5%
kill for S. aureus, 99.6% for P. aeruginosa and 98.7% for E. coli
strains.
[0203] Polyoxetanes:
[0204] Introduction.
[0205] FIG. 3 depicts one embodiment of our model in surface
modification using P[AB]-polyurethanes. It is well known that
concentration of soft blocks occur at the air-polymer interface in
polyurethanes. FIG. 3b shows copolyoxetane soft blocks as P[AB]
"bottle brushes". Copolyoxetane brushes have flexible main chains
(T.sub.g's, -40 to -60.degree. C.) and relatively short side chain
"bristles".
[0206] Designations.
[0207] Notations for base polyurethane are typified by
HMDI/BD(50)-PTMO(1000) (FIG. 3c), where HMDI is H12MDI,
(4,4'-(methylene bis-(p-cyclohexyl isocyanate)), BD is 1,4-butane
diol, and 50 is the wt % HMDI/BD hard block. FIG. 3a shows the
1,3-propylene oxide main chain and side chains that comprise P[AB]
copolyoxetane bottle brushes, "BB". A and B (and sometimes C) side
chain designations are also used for soft block repeat units. By
extension, bottle brush polyurethane modifiers (BB-U) results in
notations such as HMDI/BD(30)-P[(A)(B)-p:(1-p)-5.1], where P
denotes ring opened structures for repeat units A and B, p is the A
mole fraction, and 5.1 is the soft block M.sub.n (kDa). In ring
opening polymerization, simultaneous feed of A and B monomers gives
random copolyoxetanes (Scheme 1). In one embodiment, the P[AB]
copolyoxetanes are random copolymers so that the designation P[AB]
is used rather than P[A-r-B].
##STR00037##
##STR00038##
[0208] Model Polymer Surface Modifier, PSM.
[0209] A model PSM was investigated having a P[(3FOx)(BrOx)]
copolyoxetane soft block (2 and 3, respectively). 3FOx was
essential in that study for BrOx surface concentration. For
example, with 0.5 wt % P[(3FOx)(BrOx)-1:1] polyurethane modifier,
Br was 2.2 atom % by XPS, but Br was at the XPS detection limit
(0.1 atom %) for a control having a P[BrOx] polyoxetane soft block.
The notion of a fluorous "chaperone" for functional moiety B was
thus established.
[0210] Hydantoin PSM.
[0211] The conversion of hydantoin to chloramines
(--N--H.fwdarw.N--Cl) by bleach results in powerful oxidative
antimicrobial functionality. Chloramine functionalized surfaces
(e.g., fibers) are stable in air and even to laundering. This work
stimulated the preparation of a copolyoxetane with Hy4Ox 4 as a
precursor to chloramine function. Surprisingly, polyurethanes with
3FOx "chaperone" A and Hy4Ox B copolyoxetane soft blocks had
unprecedented wetting characteristics. The dry surface was
moderately hydrophilic with 70-80.degree. advancing contact angles
(.theta..sub.adv), while the wetted surface was hydrophobic with
.theta..sub.adv>100.degree.. This is opposite usual behavior by
which water adsorption or surface reconstruction results in
decreased contact angles.
[0212] The original goal of introducing oxidative antimicrobial
function was attained. Less than 2 wt % of the above PSM had
surface accessible N--H convertible to chloramine (N--C1) with
dilute bleach. The coatings effected rapid 100% kill of sprayed on
Gram+/-bacterial challenges.
[0213] P[(3FOx)(MEnOx)] Copolyoxetane Diols.
[0214] Both random and block [(3FOx)(MEnOx)-p:(1-p)] copolyoxetane
diols were prepared. These amphiphilic diols containing PEG-like
(ME3Ox or ME7Ox, Scheme 2) and 3FOx side chains were incorporated
in polyurethanes (FIG. 4a). P[A-r-B] and P[A-b-B] polyurethanes
were employed as PSMs for a conventional MDI/BD-PTMO base
polyurethane (FIG. 4b). Surface composition (XPS), morphology (AFM)
and wetting behavior for the respective P[A-r-B] and P[A-b-B]
polyurethane modified base polyurethane are distinctly
different.
[0215] Alkyl-Ammonium PSMs.
[0216] catheters to touch pads. Criteria were set for contact
antimicrobial elastomers and coatings: (a) no biocide leaching, (b)
stability in air and water and (c) unlike --N--Cl, low or no
cytotoxicity.
##STR00039##
[0217] Coating surface modification, which uses 1 or 2% PSM with a
conventional "base" polymer, has important and distinguishing
features that contribute to intellectual merit including (a)
retention of established bulk properties for the majority polymer
(FIG. 3b), (b) compositional economy that results from using the
P[AB]-soft block polyurethane as a minor constituent, and (c)
potential for translation to applications.
[0218] HMDI-BD(30)-P[(3FOx)(C12)-87:13-6.5] 5, shown, was generated
as a trial PSM. The matrix polyurethane HMDI/BD(50)-PTMO is shown
in FIG. 3. In a spray test, 2 wt % PSM 5 provided 100% kill against
a 10.sup.7 CFU/mL aerosol challenge of Gram(-) (P. aeruginosa, E.
coli) and Gram(+) (S. aureus) bacteria during an exposure time of
30 min (FIG. 5b). Excellent contact antimicrobial kill was
consistent with 5a surface concentration by XPS analysis.
##STR00040## [0219] Components of
HMDI-BD(30)-P[(3FOx)(C12)-86:13-M.sub.n], 5 and P[AB] soft block
5a.
[0220] Stability of 2 wt % PSM 5.
[0221] A series of HMDI/BD(30)-P[(3FOx)(C12)-86:13-M.sub.n]
modifiers with systematic changes in M.sub.n (kDa). Temporal
stability of antimicrobial effectiveness was previously evaluated.
Tests 2-3 days after drip coating reproduced previous results (FIG.
5b), but after two-weeks coatings gave widely varying results with
50% or less kill A representative result for a 2 wt %
HMDI/BD(30)-P[(3FOx)(C12)-86:14] modified coating after 2 weeks is
shown in FIG. 5d. Longer times gave worse results.
[0222] To begin understanding loss of antimicrobial function,
surface morphology was investigated by TM-AFM. 3D height images
(not shown) for 2 wt % HMDI/BD(30)-P[(3FOx)(C12)-86:14] were
observed as a function of time. Two days after coating, the image
was observed to be almost featureless. After 2 weeks multiple 2-3
.mu.m features up to .about.500 nm high appear. After 8 weeks the
surface is topologically complex with a high density of nano- and
microspike features. Loss of antimicrobial effectiveness correlates
with the observed surface phase separation of the
HMDI/BD(30)-P[(3FOx)(C12)-86:14] modifier. The phase separated
domains apparently sequester quaternary charge leading to
ineffective contact antimicrobial kill.
[0223] Zeta Potentials.
[0224] Zeta potential measurements offer a direct determination of
surface charge. Compared to the relatively slow deactivation of
quaternary charge density in air (biotesting, AFM), streaming
potential measurements indicate that water accelerates loss of
surface accessible positive charge for the series of 5-modified
polyurethanes (HMDI/BD(30)-P[(3FOx)(C12)-86:14]). The unexpected
temporal instability of quaternary charge led to a major thrust in
proposed research on stabilization strategies.
[0225] New P[AB] soft block BB-polyurethane (BB-U) modifiers with
improved temporal stability are described. In one embodiment, a
facile route to quat-surface concentration for condensation cured
PDMS is described.
[0226] The Matrix.
[0227] In one embodiment, HMDI-BD(50)-PTMO(1000) may be used as a
convenient matrix or base polyurethane. This thermoplastic
polyurethane is easily prepared (50-100 g) and unlike most tested
alternatives, does not confuse dynamic contact angle analysis (DCA,
Wilhelmy plate) by water contamination. With a high hard block wt %
HMDI-BD(50)-PTMO(1000) has a moderate strain-to-break (-400%) and a
relatively high modulus (9.7 MPa).
[0228] New Bottle Brushes.
[0229] To help thwart phase separation, new BB-U surface modifiers
based on two classes of P[AB] copolyoxetanes are described. Results
demonstrate surface concentration without phase separation for
both, and we have found that same P[AB]
##STR00041## [0230] Components of MDI/BD-P.left
brkt-top.(MEnOx)(C12). copolyoxetane diols can be used with new
bottle brush-nanoglass (BB-NG) surface modifiers described
herein.
[0231] i. PEG/Alkylammonium Copolyoxetanes,
[0232] The soft block in HMDI/BD(30)-P[(ME2Ox)(C12)-0.86:0.14] is
shown. This PSM was found highly effective in antimicrobial
testing. At short times after coating preparation, it was nearly
equivalent to the 3FOx analog 5. In this regard, the 19 atom C12
side chain acted as a "self-chaperone"; the 13 atom side chain
analog "C6" was considerably less effective in biotesting.
##STR00042##
[0233] PEG side chain length. The initial advancing contact angle
(.theta..sub.adv, DSC) for a 2 wt % blend of
HMDI/BD(30)-P[(ME2Ox)(C12)-0.86:0.14] with the
HMDI/BD(50)-PTMO-1000 base polyurethane (FIG. 2) was 94.degree.,
followed by a drop to 80.degree. in the second cycle (total time
.about.5 min).
[0234] Quat mole fraction. C12 mole fraction can increased by
increasing the BBOx 6 mole fraction in the precursor
P[(ME2Ox)(BBOx)-p:(1-p)] diols. In solution, it was found that an
optimum range of C12 mole fraction (0.4-0.6) was suitable for
biocidal kill (lowest minimum inhibitory concentration, MIC).
[0235] In one embodiment, low MICs may be obtained for 40-60 mol %
C12 in P[(ME2Ox)(C12)-p: (1-p)].
##STR00043## [0236] Components of IPDI/BD(40)-P[4FOx].
[0236] ##STR00044## [0237] Model for amphiphilic behavior of soft
block P(4FOx).
[0238] 4FOx/Alkylammonium Copolyoxetanes.
[0239] With long fluorous side chains (.gtoreq.C.sub.f8,
C.sub.f=perfluorinated carbon), replacement of terminal --CF.sub.3
by --CF.sub.2H results in decreased surface tension. For
fluoromethacrylate block copolymers having "short" side chains
(<C.sub.f8) a similar reduction of .theta..sub.adv and
.theta..sub.rec is observed; low contact hysteresis was attributed
to above-ambient T.sub.g's.
[0240] Compared to methacrylates, completely different wetting
behavior is observed for a polyurethane with the 4FOx polyoxetane
soft block shown. A striking feature for IPDI/BD(40)-P(4FOx) is
.theta..sub.adv.about.108.degree. (like --CF.sub.3) but
.theta..sub.rec.about.40.degree., resulting in a large contact
angle hysteresis (.theta..sub.A=68.degree.). The model shown may
account for the amphiphilic behavior of the P(4FOx) polyurethane.
In air, enthalpically driven H-bonding of CF.sub.2H to ether
moieties is believed to result in --CF.sub.2--CF.sub.2-- groups
dominating the surface. XPS is consistent with this view. Hydrogen
bonding may account for the 40.degree. .theta..sub.rec.
[0241] Coatings with 2 wt % HMDI/BD(30)-P[(4FOx)(C12)-p:(1-p)] were
prepared, where 4FOx to C12 ratios were 86:14 and 66:34. Zeta
potentials and contact kill against PA, P. aeruginosa, by the spray
test described herein show that the zeta potential is higher for
the modifier with 34 mol % C12 (92.1 mV) compared to that for the
one with 14 mol % C12 (68.2 mV). Importantly, the zeta potential
was nearly the same (.+-.1 mV) over the course of two runs for each
of the two modified coatings (2.times.20 min.apprxeq.40 min,
10.sup.-3 M KBr). In keeping with the
##STR00045## [0242] Components of 4FOx modifier
HMDI/BD(30)-P[(4FOx)(C12)-p:(1-p)]. high positive zeta potentials,
high contact kill against PA was observed for both coatings.
[0243] The "bottle brush-nanoglass" (BB-NG) surface modification
includes two principle components: (a) a polyoxetane BB with
triethoxysilyl end groups and (b) an alkoxysilane that together
with BB chain ends comprise precursors to a "nanoglass", NG phase
via hydrolysis and condensation reactions.
[0244] One embodiment of the BB-NG concept is illustrated in FIG. 6
with a P[AB] copolyoxetane soft block brush (see also FIG. 2). We
have found that BB-NG surface modification is broadly applicable,
as any P[AB] copolyoxetane diol or other diol can be quickly and
easily converted in one step to a BB 7-analog. The BB-NG concept is
related to the use of glass and/or silicon wafers for growing
functional thin films such as by controlled radical polymerization.
For BB-NG the nanoglass domains are generated in situ from alkoxy
end functionalized brushes and an alkoxysilane nanoglass
precursor.
[0245] For P[AB] copolyoxetanes, P[(ME2Ox)(C12)] and P[(4FOx)(C12)]
diols are easily converted to 7-analogs and in turn to modified
base polyurethanes.
[0246] A conversion of P[(4FOx)(C12)-64:24] diol to a 7-analog was
carried out. This reaction to form the 7-analog designated 9 is
shown in FIG. 6. This was followed by (b) modification of base
polyurethane (FIG. 2) with 1 wt % 9 and bis(triethoxysilyl)ethane
("BTSE") (10 wt %). Biotesting with sprayed-on P. aeruginosa (1 hr
residence) confirmed feasibility with 100% kill. Two weeks later
with tests in triplicate, 100% kill was once again realized
indicating good temporal stability in air. This is surprising
because (a) it demonstrates the general reaction of a P[AB] diol to
form a 7-analog (namely 9) and (b) the surface modification of a
conventional polyurethane "delivers" quaternary antimicrobial
function that is stable with time, which is in contrast to the
instability of the conventional polyurethane modifier
HMDI-BD(30)-P[(3FOx)(C12)-86:13-M.sub.n]. Preliminary results
suggest somewhat better stability than even the much-improved 4-FOx
based polyurethane modifier HMDI/BD(30)-P[(4FOx)(C12)-p:(1-p)]. In
this regard, an important practical advantage is achieved by
P[(4FOx)(C12)]-TES 9, which is also much simpler to prepare and has
good solubility.
[0247] If desired, varying wt % of NG can be achieved with
increasing increments of BTSE.
[0248] In one embodiment, the BB-NG modifier may be adapted to
other polymers such as acrylates seems likely. P[(ME2Ox)(C12)]-7
analogs will be soluble in alcohol-water mixtures while 4FOx-based
precursors will be soluble in alcohols.
HO--P(3FOx)-OH+HMDI.fwdarw.HMDI-U-P(3FOx)-U-HMDI(I-1) Eq 1
I-1+H.sub.2N(CH.sub.2).sub.3--PDMS-(CH.sub.2).sub.3NH.sub.2.fwdarw.[H.su-
b.2N(CH.sub.2).sub.3--PDMS-UR-HMDI]-P(3FOx)-U-HMDI_UR-PDMS-(CH.sub.2).sub.-
3NH.sub.2(I-2) Eq 2
I-2+OCN--(CH.sub.2).sub.3--Si(OEt).sub.3.fwdarw.I-2[UR-(CH.sub.2).sub.3--
-Si(OEt).sub.3].sub.2(I-3) Eq 3
Scheme 3.
[0249] "One pot" end-capping reactions with dibutyltin diacetate
catalysis giving condensation curable PDMS-3FOx-PDMS block
copolymer I-3; U, urethane; UR, urea.
[0250] Surface Modification of Polydimethylsiloxane (PDMS).
[0251] Translation to applications is strongly inhibited by the
presence of a C.sub.f8 component that could degrade to
perfluorooctanoic acid (PFOA), which is bioaccumulative. Therefore,
the preparation of the hybrid triblock copolymer, PDMS-P(3FOx)-PDMS
is noteworthy as a "Cf-1 modifier. In one embodiment, the
introduction of P[3FOx], 2, provides a "C.sub.f1" modifier that is
not a PFOA precursor.
[0252] A one pot three step reaction generates the condensation
curable PDMS-3FOx-PDMS triblock I-3 (Scheme 3). Dibutyltin
diacetate catalyzes urethane, urea, and condensation cure. Cured
I-3 coatings show no hint of fluorous (oleophobic) surface
properties. XPS and contact angles are identical to a PDMS
control.
[0253] Although the condensation cured triblock I-3 has a PDMS-like
surface, at low wt % I-3 triblock might modify a PDMS elastomer
creating a fluorous surface. Previously, isopropanol was used to
differentiate PDMS (0.degree. contact angle) from fluorous C.sub.f8
(30-80.degree.) surfaces. In a pilot study, condensation cured PDMS
coatings with 0.1-2 wt % I-3 had contact angles of
.gtoreq.20.degree. with isopropanol as a probe liquid indicating a
fluorous surface component. The contact angle decreased to
5.degree. at 10 wt % suggesting P(3FOx) phase
separation/aggregation that depletes fluorous surface
concentration.
[0254] The fluorinated polyoxetanes P(3FOx) and P(5FOx) described
herein may be obtained from OMNOVA Solutions, Akron Ohio.
EXAMPLES
Example 1
Polyurethane Purification
[0255] In a 60 mL vial, 30 grams of methanol and 6 grams of THF
were mixed. Into the vial, 3 grams of polyurethane pellets
(Lubrizol Estane ALR-E72A) was added. The mixture was then heated
to 60.degree. C. PU pellets swell to at least double their original
size within one hour, which further coalesced into one piece
overnight.
[0256] Every 24 hours, a sample was taken and dried under vacuum to
remove solvents. A few dried pellets were soaked in clean water
that was confirmed by pre-interrogation water check with flamed
glass slide and dynamic contact angle (DCA, Wilhelmy plate,
degrees). After at least 5 minutes of soaking the purified
polyurethane pellets, the water was checked with DCA using a flamed
glass slide to determine whether contamination is present (i.e.,
small molecule or surface active molecules leaching out of the
purified polyurethane). After at least 5 minutes of soaking, a
water check with DCA and flamed glass slide is done to check
whether contamination is detected. Samples were checked at 24, 48,
72, and 96 hour. The results (not shown) indicate that for PU
pellets soaked in methanol/THF mixture for 96 hours, water
contamination is negligible after 96 hours.
Example 2
Polyurethane Purification
[0257] In a 200 mL vial, 100 grams of ethanol and 20 grams of THF
were mixed. Into the vial, 10 grams of polyurethane pellets
(Lubrizol Estane ALR-E72A) was added. The mixture was then heated
to 30.degree. C. PU pellets swell to at least double of its
original size within 24 hours. The pellets were soaked for 2 weeks
and no significant coalescence was observed. Ten pellets were taken
out and dried under vacuum to remove solvents. Five dried pellets
were soaked in clean water that was confirmed by pre-interrogation
water check with flamed glass slide. After at least 5 minutes of
soaking, a water check with flamed glass slide showed no water
contamination.
Example 3
Synthesis and Characterization of Blends of HMDI/BD
P[(3FOx)(C12)
[0258] Materials
[0259] Synthesis of Monomers:
[0260] Synthesis of 4FOx:
3-Methyl-3-(2,2,3,3,-tetrafluoropropoxymethyl)oxetane, 4FOx, was
synthesized by replacing Br in BrOx with fluorinated alcohols using
phase transfer catalysis (TBAB). A typical synthesis involved
reacting 41.25 g (250 mmol) of BrOx with 46.2 g (350 mmol) of
2,2,3,3,-tetrafluoropropan-1-ol with in presence of TBAB (5 g,
0.0125 mmol). The mixture was heated to 60.degree. C. in 20 ml of
water. KOH (15.78 g, 87%) was dissolved in water (20 ml) and added
drop wise over one-hour period. This solution was then heated to
75.degree. C. and stirred for 72 hr. The resulting 4FOx is
separated from the aqueous layer using dichloromethane. The
resulting dichloromethane solution was dried with magnesium sulfate
and dichloromethane evaporated using a rotovap. GC-MS showed a
small percentage of BrOx. Short path distillation gave 99%+4FOx
monomer.
[0261] Synthesis of BBOx: The precursor to BBOx (Bromobutyl
oxetane) is 3-(hydroxymethyl)-3-methyl oxetane (HOOx) which was
prepared via the pyrolysis of diethyl carbonate and 1,1,1
tris(hydroxymethyl)ethane as described in the literature. BBOx was
prepared from HOOx and dibromobutane via a phase transfer catalysis
reaction and is also described in the literature.
[0262] Preparation of P[AB] diol: The P[AB] diol is prepared via
cationic ring opening polymerization following the process
described previously. Two different diols of varying 4Fox:C12 ratio
were prepared to study the effect of changing the amount of
quaternary ammonium on the antimicrobial properties of the surface
modifier. The two different diols obtained were
P[(4FOx)(BBOx)-0.86:0.14] and P[(4FOx)(BBOx)-0.66:0.34]. Molecular
weights of the two diols were calculated using NMR end group
analysis. These diols were then quaternized by the substitution of
C--Br with N,N dimethyl dodecyl amine (C12) in acetonitrile for 18
hours. The diols are then used as soft blocks for making
polyurethanes using the soft block first method, were the ratio of
the hard block to soft block was 30:70 (wt/wt).
[0263] The base polyurethane was synthesized using a two-step
solution polymerization, using PTMO (1000) as soft block and
HMDI-BD as the hard block (50 wt %).
[0264] Preparation of Blends and Coatings:
[0265] 2, 1, and 0.5 wt % blends of the surface modifier in base
polyurethane were prepared. It was observed that unlike the 3FOx
based P[AB] polyurethane, the 4FOx based polyurethanes were
insoluble in THF. DMAC (dimethyl acetamide) was used as an
alternative solvent. Blends of the PSM in DMAC and base
polyurethane in THF produced fairly transparent coatings. However,
over a period of 7 days, the surface modifier was observed to be
phase separating out of the blends. This prompted the use of DMAC
as a solvent for the entire blend. Coatings were prepared by drip
coating glass slides and glass cover slips with the blend. Due to
the low volatility of DMAC, the coatings had to be heated in an
oven at 120.degree. C., overnight. Transparent coatings were
obtained.
[0266] Characterization:
[0267] X-Ray Photoelectron Spectroscopy: XPS spectra were studied
for both 4FOx and 8FOx Polyurethanes. The measurements were carried
out on the Thermo Fisher Scientific ESCALAB 250 "X-ray
Photoelectron spectrometer". This instrument has monochromatized A1
K .alpha. X-ray and low energy electron flood gun for charge
neutralization. X-ray spot size for these acquisitions was on the
order of 500 mm. Pressure in the analytical chamber during spectral
acquisition was less than 2.times.10-8 Torr Pass energy for survey
spectra was 150 eV. The take-off angle was 90.degree.. The data
were analyzed with the Thermo Avantage software (v4.40). Samples of
2, 1 and 0.5 wt % blends were cut and attached to the sample holder
using carbon tape.
[0268] Atomic Force Microscopy: Morphological analyses of
polyurethane surfaces were carried out using a Dimension-3100
(Digital Instruments, CA) atomic force microscope with a NanoScope
V controller. Imaging was performed in tapping mode using a
microfabricated silicon cantilever (40 N/m, Veeco, Santa Barbara,
Calif.) in air. Images were analysed using the Nanoscope v710
software.
[0269] Zeta Potential: The electrokinetic analyzer in surface
analysis or SurPASS from Anton PAAR was used to investigate the
zeta potential of the coated surfaces based on a streaming
potential and streaming current measurement. The Zeta Potential is
measured using the Helmholtz-Smoluchowski method.
[0270] Bactericidal Test: Bacterial spray testing has been used in
other studies of non-leaching biocidal materials and was used
herein to determine biocidal activity of the P[(4FOx)(C12)] PSM
blend.
[0271] Agar plates were streaked with the desired bacteria from a
stock culture kept frozen at -70.degree. C. and incubated at
37.degree. C. for 18-24 hrs. From this plate a single colony was
collected and used to inoculate 10 mL of luria broth. This culture
solution was incubated for 18-24 hrs at 37.degree. C. After
incubation, the 1:50 dilution of the culture was prepared and
incubated at 37.degree. C. until an optical density of 0.2-0.3 was
observed for 1 mL of culture. Once the desired optical density has
been achieved, the culture solution is used in bacteria
challenges.
[0272] A biocidal test was devised to deposit the bacterial
solution via an aerosol spray. Using as stock bacteria
concentration of 10.sup.6 colony forming units (CFU)/mL, slides
coated with 2 wt % and 1 wt % PSM blends where spray for 1 second
and weighed to determine the amount of bacteria solution deposited.
Sprayed slides were then placed in a constant humidity (85-95%)
environment. Keeping the samples at constant humidity is important
because control experiments in ambient air showed irreproducible
fractions of dead bacteria as a function of time which is likely to
the bacteria experiencing osmotic shock. After 60 min, the slides
were placed in saline solution and vortex stirred for 2 min. One
hundred microliter aliquots and (.times.10) dilutions were removed
and spread onto agar plates that were incubated at 37.degree. C.
for 18 h. After incubation, bacteria colonies were counted to
obtain the percent kill.
[0273] Results and Discussion:
[0274] We have developed antimicrobial polymeric coatings without
affecting the bulk properties of the polymer which retain their
antimicrobial properties over a period of time. All the samples
were studied for changes in morphology both immediately after
coating and also four weeks after coating. The results obtained
would be an indicator of how the coatings would perform in real
life conditions. Quantifying surface accessible charge of 3FOx
based polyurethane coatings by the microfluidic capillary method
has shown that a 2 wt % coating of HMDI/BD(30)-P[(3FOx)(C12)-86:14]
had a sharp fall in the surface accessible positive charge within
80 seconds. This had explained the loss in antimicrobial properties
of the 3FOx based coatings when tested after two weeks of preparing
the coatings.
[0275] X-Ray Photoelectron Spectroscopy:
[0276] The coatings of the blends were studied by XPS to understand
the surface composition. A survey spectrum for each of the blends
confirmed the presence of carbon, oxygen, fluorine and nitrogen.
Table 1 gives comparison between the calculated and observed atom
percentages of the four elements. The calculated percentage assumes
100% surface modifier soft block on the surface.
[0277] Zeta Potential measurements: 2 wt % blends of both
HMDI/BD(30)-P[(4FOx)(C12)-66:34-5.7] and
HMDI/BD(30)-P[(3FOx)(C12)-86:14-4.2] were prepared and tested for
their zeta
TABLE-US-00001 TABLE 1 Calculated vs observed atom percentages of
0.5, 1 and 2 wt % blends of surface modifier. Observed atom % No of
atoms Calculated Surface modifier percentage in blend in soft block
atom % 0.5 1 2 C 13.1 72% 67% 68% 65% O 2 11% 20% 21% 19% F 2.64
15% 10% 9% 13% N 0.34 2% 3% 3% 3%
potential values. The results obtained are summarized in Table
2.
[0278] We found that increasing the percentage of C12 in the
polyurethane imparted a higher
TABLE-US-00002 TABLE 2 Zeta potentials for 2 wt % HMDI/BD(30)-
P[(4FOx)(C12)-p:(1-p)] P 1-p .zeta. (mV) 86 14 68.2 66 34 92.1
positive charge on the surface. Antimicrobial tests were also
carried out on these two coatings and the results showed that while
the HMDI/BD(30)-P[(4FOx)(C12)-66:34-5.7] showed a 100% kill of
bacteria, HMDI/BD(30)-P[(3FOx)(C12)-86:14-4.2] caused 90% kill.
Based on these preliminary data, detailed Zeta Potential
measurements were carried out for 2, 1 and 0.5 wt % blends of
HMDI/BD(30)-P[(4FOx)(C12)-66:34-5.7]. The results obtained are
summarized in FIG. 7.
[0279] The results show a very clear distinction in the surface
accessible positive charge for the 2, 1 and 0.5 wt % of the blends.
It is believed that the fluorous side chain of the soft block acts
as a chaperone for the quaternary ammonium side chain to be on the
surface, hence, increasing the amount of C12 increases the positive
charge on the surface. A surprising observation is that the 2 wt %
blend gives positive zeta potential values even after 3 hours of
exposure to the electrolyte. This is a significant improvement over
what had been previously observed for the 2 wt % coatings of
HMDI/BD(30)-P[(3FOx)(C12)-86:14].
[0280] The coatings were again tested after 4 weeks to see if they
had lost the surface accessible positive charge. The results are
summarized in FIG. 8.
[0281] Atomic force microscopy--To understand the surface
morphology with changing surface modifier concentration, TM-AFM
images of 0.5 wt %, 1 wt % and 2 wt % blends were obtained. The
images were obtained at a setpoint ratio of 0.9 and an area of 25
.mu.m.times.25 .mu.m was investigated. The images (not shown) were
obtained within one week of coating of the samples. It was observed
that surface roughness increases with increasing percentage of
surface modifier in the blend. In previous studies of evolving
surface morphologies of HMDI/BD(30)-P[(3FOx)(C12)-86:14], it was
shown that not only does the surface phase separates within three
to four days of preparing the coatings, but the phase separation is
extremely dynamic with micropeak like features appearing and
multiplying on the surface over a period of time, and within 8
weeks of coating the surface is completely covered with these
features.
[0282] To analyze the surface stability of the new coatings, the
samples were investigated under similar conditions and the images
obtained (not shown) show no significant change in the surface
morphology over time, which is surprising.
[0283] Antimicrobial tests: Antibacterial tests were performed on
the three different concentrations of the blend. The results are
shown in FIGS. 9 and 10.
Example 4
Blends of P[4FOx:C12-66:34] Diol BTSE Hybrid
[0284] Polymer surfaces modified with polyurethanes containing
P[(3FOx):(C12)m:n] polyoxetane soft blocks (where 3FOx is a
trifluoroethoxy side chain and C12 is the quaternary ammonium
containing side chain) have the ability to kill bacteria via
non-leeching contact kill. However, further research showed the
dynamic nature of these surfaces and the antimicrobial property was
found to be diminished over time. Streaming potential studies on
these surfaces showed the rapid lowering of surface accessible
positive charge from 140 mv to 85 my within a period of 80 seconds
for a 2 wt % blend. Changing the fluorinated side chain from a
--CF.sub.3 group to a --CF.sub.2CF.sub.2H group was found to be an
effective solution for increasing the stability of the positive
charge on the surface. It was however observed that although the
change in the fluorinated side chain remarkably improved the
surface stability of positive charge, it did not completely "lock"
the positive charge on the surface. Zeta potential studies showed
the diminishing positive charge of about 10 mv over a period of 3
hours for a 2 wt % blend of polymer surface modifier with base
polyurethane. The antimicrobial property, which was excellent (100%
kill) for surfaces tested within 1 week of preparation of the
blend, was found to be reduced over a period of one month. Hence a
simple modification of the surface was tested to stabilize the
charge on the surface by restricting the movement of the side
chains. Guided by the fact that surface modifier polyurethanes made
from P[(4FOx)(C12)-66:34] showed good antimicrobial properties, it
was decided to test the concept with the same diol.
[0285] Experiment:
[0286] Materials: P[4FOx:C12-66:34] diol was prepared according to
the method discussed earlier. 3-isocyanatopropyltriethoxysilane
(SII 6455) and bis(triethoxysilyl)ethane (SIB 1817, BTESE) were
purchased from Gelest, Inc. Dibutyltin diacetate was used as a
catalyst and was purchased from Aldrich. Tetrahydrofuran, 99.6%,
(for analysis ACS, stabilized with BHT) was obtained from
Acros.
[0287] The reaction takes place in two steps:
[0288] FIG. 11 gives a schematic of step 1 of the preparative
procedure:
[0289] In step 1, the diol is end-capped with
isocyanatopropyltriethoxysilane. A 1:2 molar ratio of diol and the
silane is used as the reactant. A solution of isocyanatopropyl
triethoxysilane in THF was prepared in a 100 ml round bottom flask
in the presence of DBTDA (0.5 wt %) catalyst (Solution A). The
solution of the diol in THF was added dropwise to solution A under
dry nitrogen purge. The disappearance of the isocyanate peak was
studied at intervals to ensure 100% endcapping of the diol.
[0290] Step 2 includes of preparation of three different blends of
the endcapped diols with base polyurethane. In the first step,
calculated quantities of the end capped diol is added to an
alkoxysilane (BTSE). The latter, together with end caps are
precursors to the "nanoglass" domain via hydrolysis and
condensation reaction. The solutions were then added to a 20 wt %
solution of base polyurethane in THF.
[0291] Three different blends of base polyurethane with 0.5, 1 and
2 wt % endcapped diol were prepared. 10 wt % BTSE was added in each
case.
[0292] Base polyurethane for this reaction was synthesized using a
two-step solution polymerization, using PTMO (1000) as soft block
and HMDI-BD as the hard block (50 wt %).
[0293] Coatings with the resulting solution were prepared within 15
min of Step 2. Microscope slides and glass cover slips were drip
coated for zeta potential, AFM measurements and antimicrobial tests
respectively. Dip coated slides were prepared for studying wetting
behavior of samples via dynamic contact angle measurements.
[0294] Cure was overnight at ambient temperature followed by
100.degree. C. for 24 hr.
[0295] Zeta Potential measurements: The electrokinetic analyzer in
surface analysis or SurPASS from Anton PAAR was used to investigate
the zeta potential of the coated glass slides based on a streaming
potential and streaming current measurement. The electrolyte used
was 0.1 mmol NaBr solution. The choice of electrolyte was governed
by the presence of a common anion (Br.sup.-) in the polyurethane so
that secondary factors such as anion exchange do not interfere with
the results.
[0296] Bactericidal Test: Bacterial spray testing has been used in
other studies of non-leaching biocidal materials and was the used
to determine biocidal activity of the P[(4FOx)(C12)] PSM blend.
[0297] Agar plates were streaked with the desired bacteria from a
stock culture kept frozen at -70.degree. C. and incubated at
37.degree. C. for 18-24 hr. From this plate a single colony was
collected and used to inoculate 10 mL of Luria broth. This culture
solution was incubated for 18-24 hr at 37.degree. C. After
incubation, the 1:50 dilution of the culture was prepared and
incubated at 37.degree. C. until an optical density of 0.2-0.3 was
observed for 1 mL of culture. Once the desired optical density has
been achieved, the culture solution is used in bacteria
challenges.
[0298] A biocidal test was devised to deposit the bacterial
solution via an aerosol spray. Using as stock bacteria
concentration of 10.sup.6 colony forming units (CFU)/mL, slides
coated with 2 wt %, 1 wt % and 0.5 wt % blends where sprayed for 1
sec and quickly weighed to estimate the amount of bacteria solution
deposited. Sprayed slides were then placed in a constant humidity
(85-95%) environment. Keeping the samples at constant humidity is
important because control experiments in ambient air showed
irreproducible fractions of dead bacteria as a function of time
which is likely to the bacteria experiencing osmotic shock. After
60 min, the slides were placed in saline solution and vortex
stirred for 2 min. One hundred microliter aliquots and (.times.10)
dilutions were removed and spread onto agar plates that were
incubated at 37.degree. C. for 18 h. After incubation, bacteria
colonies were counted to obtain the percent kill.
[0299] Results and Discussion:
[0300] Atomic Force Microscopy:
[0301] A study of the topology and morphology provides an idea of
the extent of phase separation, if any, of the blends and hence can
provide important information about their performance over a period
of time. Images (not shown) were taken at a setpoint ratio
(r.sub.sp) of 0.9 with a scan size of 25 .mu.m. Two sets of images
were studied to observe the change in the morphology of the
surfaces with time. Images of surfaces of the blends obtained
within 1 wk of coating indicated near surface phase separation for
all the three blends with the 1 wt % blend exhibiting maximum
roughness. The size of phase separated features is observed to be
increasing with the increase of the percentage of surface modifier
in the blend.
[0302] X-Ray Photoelectron spectroscopy: Elemental composition of
the surface was studied with the help of X-Ray photoelectron
spectroscopy. Table 3 with the calculated and observed percentages
of the elements is given below. The calculated percentage assumes
100% of the fluorinated diol to be on the surface irrespective of
the composition of the blend.
TABLE-US-00003 TABLE 3 Calculated vs observed atomic percentages of
elements on the surface of blends Calculated composition Observed
composition (at %) of blends (at %) Soft Block only Hybrid 0.5 1 2
O 11.06 19.4 25.97 20.74 23.29 C 72.46 58.48 56.85 63.42 59.03 F
14.6 7.32 4.64 6.97 8.55 Si 0 8.31 11.6 7.39 7.41 N 1.88 6.49 0.94
1.48 1.73
[0303] From the above data it is observed that the observed
percentage of nitrogen is lower than the calculated amount. It is
also observed that increasing the percentage of the surface
modifier diol increases the availability of nitrogen on the
surface.
[0304] Zeta Potential:
[0305] Measuring and relating surface accessible positive charge to
the antimicrobial property of a blend is a unique and much less
time consuming process that helps assess not only the bactericidal
property of a blend but also the durability of the blend. The
presence of quaternary ammonium on the surface was already
confirmed by XPS. Stability of the positive charge on the surface
was studied by analyzing the surface by continuous flow of
electrolyte for a period of 3 hours. The results are shown in FIG.
12.
[0306] The zeta potential values show excellent stability of the
blends over time. For the 2 wt % blend the zeta potential remains
almost constant for a period of three hours within which eight
individual runs of 2 cycles each were carried out. Zeta potential
increases about by about 7 mV for 1 wt % blends while the 0.5 wt %
blend proves to be only slightly better than a control sample of
base polyurethane. This explains the absence of measurable
quaternary ammonium nitrogen for the 0.5 wt % blend as observed by
XPS.
Example 5
Quaternary Ammonium Modified Silicones
[0307] Materials.
[0308] Hydroxyl terminated polydimethylsiloxane (DMS-S21, 90-120
cSt, 4 kDa), 3-chloropropylmethyldimethoxysilane (SIC 2355) and
bis(triethoxysilyl)ethane (SIB 1817, BTESE) were purchased from
Gelest Inc. N,N-dodecyldimethylamine (C12) and dibutyltin diacetate
were obtained from Aldrich. Tetrahydrofuran, 99.6%, (for analysis
ACS, stabilized with BHT) was obtained from Acros. Modified fumed
silica nanoparticles (T-FSN, Cab-o-sil TS530 HMDZ treated fumed
silica) having a BET surface area of 200 m.sup.2/g was generously
provided by Quantum Silicones, Midlothian, Va.
[0309] Quaternary Ammonium Modifier (QAM/SMA 1) Synthesis.
[0310] With reference to FIG. 13, synthesizing the modifier
involves a single step. A substitution reaction occurs between
3-chloropropylmethyldimethoxysilane 1 and N,N-dodecyldimethylamine
2 to incorporate the quaternary charge.
[0311] A typical precursor synthesis involves reacting 5 g (27.4
mmol) of reactant 1 with 5.5 g (25.8 mmol) of the tertiary amine 2
in a reaction vessel at 30.degree. C. for 48 hrs. The reaction was
carried out in the presence of .about.25 ml of THF as a solvent. A
constant purge of dry nitrogen was maintained inside the reaction
vessel to eliminate the presence of any moisture since the methoxy
functional groups present in 1 are susceptible to hydrolysis. The
reaction of 1 with 2 provided the QAM 3 in quantitative yield. A
complete substitution of the chlorine atom by the C12 tertiary
amine was characterized by .sup.1H-NMR and FT-IR spectroscopy. The
modifier was stored below room temperature inside a properly vacuum
sealed container to prevent hydrolysis of the alkoxy functional
groups.
[0312] Coating Preparation.
[0313] Coatings were prepared on microscope slides by adding
varying weight percents of the QAM to a silanol terminated PDMS
following a condensation cure. PDMS coatings with 0.5%, 1% and 2%
(by weight) of the modifier were prepared for further
characterization. The modified coatings have been designated as
P-x, where, `P` stands for the 4 kDa poly(dimethylsiloxane) and `x`
refers to the wt % of the surface modifier incorporated in the
coating. Preparation of a typical 0.5 wt % modified PDMS (P-0.5)
coating involves adding 0.025 g of the QAM 3 to 5 g of a 4 kDa
silanol terminated PDMS. The resin was mixed in high shear
equipment (Speed Mixer) at 2700 rpm for 4 times at 60
seconds/cycle. A transparent, homogenous resin was obtained to
which 0.25 g (5 wt %) of the crosslinker, BTESE along with 0.5 wt %
of DBTDA catalyst was added. The resulting resin was again mixed in
high shear equipment at 2700 rpm for 3 times at 60 sec/cycle.
Microscope slides were drip coated with the resin and was kept at
ambient (.about.25.degree. C.) overnight to initiate the formation
of crosslinks. The condensation cure process was driven to
completion by keeping the coated microscope slides at 100.degree.
C. for 24 hr. Plaques were formed by pouring the resin into PTFE
plates and following the same curing technique (FIG. 14).
[0314] A representative PDMS coating reinforced with 10 wt % of
fumed silica nanoparticles was synthesized to investigate the
effect of adding fillers on surface and bulk properties. Treated
fumed silica nanoparticles (0.5 g, 10 wt %) was added to 5 g of the
4 kDa poly(dimethylsiloxane) and mixed in a high shear equipment at
2700 rpm for 60 sec. The cycle was repeated for 4 more times to
obtain a homogenous resin. The remaining process is identical to
that described in the above paragraph. These samples are designated
as PR-x, where `PR` stands for reinforced PDMS and `x` denotes the
wt % modifier.
[0315] Characterization.
[0316] Infrared Spectroscopy.
[0317] FT-IR spectra were obtained using a Nicolet 400 FT-IR
spectrometer. A background spectrum was taken before running each
sample and 32 scans were taken from 500 to 4000 cm-1. The spectra
were analyzed using Omnic software.
[0318] NMR spectroscopy.
[0319] .sup.1H-NMR (Varian Mercury 300, 283 MHz) spectra were used
to qualitatively confirm the complete substitution of the chlorine
atom from 1, followed by quaternisation. Spectrum for QAM samples
dissolved in chloroform-d was obtained for 32 scans.
[0320] Antimicrobial Assay.
[0321] Bacterial strains of Pseudomonas aeruginosa (PAO1),
Staphylococcus aureus (ATCC-25904) and Escherichia coli
(DH5.alpha.) were used for investigating the biocidal activity of
P-0.5, P-1 and P-2 coatings. Condensation cured PDMS elastomer
(P-0) was used as a control for this study. Bacterial cultures were
streaked on Luria Agar plates from frozen stocks and incubated
overnight at 37.degree. C. A single colony from each strain was
used to inoculate 6 ml of Luria Broth (LB) and grown overnight at
37.degree. C., 225 rpm. A starting inoculum of 10.sup.8-10.sup.9
colony forming units per milliliter (CFU/ml) of the desired
pathogen was used for the culture. Aliquots from the overnight
culture were taken and reinoculated in LB in a 1:100 dilution.
[0322] A biocidal test was devised to simulate aerosol deposition
(cough, sneeze) of pathogenic bacteria. With a sprayer designed to
deliver a controlled volume (or weight), a challenge of the
bacterial culture (.about.10.sup.7 CFU/mL) was delivered to the
surface of the coated samples. A constant weight of .about.6 mg of
the bacterial culture was sprayed on the coated microscope slides.
The coated slides were placed in a humidified chamber (85-95%)
environment, since a constant humidity is important because control
experiments at ambient air showed irreproducible fractions of dead
bacteria as a function of time. This step anticipates future
studies for estimating kill kinetics. After 30 min residence time,
the slides were placed in saline solution and vortexed for 2 min.
An 100 .mu.l aliquot and a 1:100 dilution were removed and spread
onto agar plates that were incubated at 37.degree. C. for 18 h.
Live bacteria (cfu's) on plates were counted to obtain the percent
kill and log reduction. The same protocol was followed for
microscope slides coated with conventional condensation cured PDMS
that served as a control for this study. Kinetics of kill was
determined by altering the residence time to 15 and 45 min.
[0323] Mechanical Test.
[0324] For tensile testing, samples were stamped out of cast
plaques, which were measured for thickness, width and gauge prior
to mounting in the RSA III tensile clamps. Data acquisition rate
was 1 Hz while the initial sample elongation rate was 10 mm/min.
The maximum elongation at break was determined for different
samples.
[0325] Results and Discussion.
[0326] Quaternary Ammonium Modifier (QAM) Synthesis.
[0327] The QAM was synthesized by following a substitution reaction
between 3-chloropropylmethyldimethoxysilane 1 and
N,N-dodecyldimethylamine 2 leading to quaternization of the
ammonium moiety. The presence of alkoxy functional groups in 1
increases its susceptibility towards hydrolysis. As a preventive
measure, both inner and outer walls of the reaction vessel were
properly flamed to eliminate the presence of any adhered water
molecules. The reaction was carried out in a moisture controlled
environment by having a continuous supply of dry nitrogen through
the reaction vessel. Generally, a quaternisation reaction is
performed at higher temperatures (.about.60.degree. C.), but this
reaction was carried out at a temperature close to ambient
(.about.30.degree. C.) in order to protect the methoxy groups from
hydrolysis.
[0328] Formation of the quaternary ammonium modifier was monitored
and confirmed by .sup.1H-NMR and IR spectroscopic analysis.
[0329] Coating Preparation.
[0330] As shown in FIG. 14, coating preparation involved
condensation cure reaction between: (1) PDMS and QAM, (2) PDMS and
BTESE (crosslinking agent) and between BTESE moieties themselves.
Low weight percent modifier (0.5%, 1% and 2%, by weight) were used
in the coatings. FIG. 14 demonstrates a condensation cure
technique, where water is both a reactant and a product. The
surface modifier was physically mixed with the hydroxyl terminated
PDMS, which ensured incorporation of the modifier in the linear
siloxane chain due to its difunctional methoxy groups. To further
facilitate formation of crosslinks, an additional amount of BTESE
(5 wt %) was added. Condensation reaction proceeds in the presence
of trace amounts of catalyst, DBTDA (0.5 wt %) to form a slightly
viscous resin. Microscope slides were drip coated and kept in the
ambient overnight to initiate the formation of crosslinks. Finally,
the condensation reaction was driven to completion by placing the
slides at 100.degree. C. for 24 hour. The resultant coatings were
optically transparent.
[0331] Antimicrobial Assay.
[0332] Having established the presence of positive charges at the
polymer-air interface, the antimicrobial activity of these coatings
was investigated against both Gram positive and Gram negative
strains of bacteria. Antimicrobial activity of the modified samples
was tested for a residence time of 30 min. As compared to the
control (P-0) which had 118 and 331 cfu for S. aureus and P.
aeruginosa respectively, P-0.5 showed biocidal activity by
affecting 68% kill against S. aureus and 75% against P. aeruginosa
in 30 min. Increasing the amount of surface modifier to 1% (for
P-1) led to an enhancement in biocidal activity to 99.5% (SA),
99.6% (PA) and 98% (EC) as seen in FIG. 15. Within experimental
error, the same extent of bacterial kill was achieved on increasing
the amount of QAM to 2% (P-2). Log reductions in bacterial cfu's
follow the same trend, with the P-1 having comparatively higher
values than P-2 for all three strains (FIG. 15).
[0333] The biocidal test result complies well with the observed
streaming potential measurements, where P-2>P-1>P-0.5>P-0.
It is believed that increasing the weight percent of the quaternary
ammonium surface modifier leads to an increase in the fraction of
cationic groups at the surface, which would translate to an
enhanced biocidal activity. In the present study, the biocidal
activity increased from P-0.5 to P-1 whereas, and increasing the
concentration of the surface modifier from 1% to 2% (P-2) affects
the same extent of bacterial kill (FIG. 15). The results
demonstrate that an optimum biocidal activity is achieved at a
modifier concentration of 1% (P-1), after which the antimicrobial
effectiveness stabilizes even though there is an increase in the
surface charge density.
[0334] FIG. 16 shows the remnant number of bacterial CFUs from
antimicrobial assays performed on different modified coatings and
the control.
[0335] Kill kinetic assay was performed in order to determine the
dependence of biocidal activity on residence time. A representative
P-1 coating affected >99% kill on strains of SA, PA and EC in
the first 15 min (FIG. 17). The P-1 coatings show remarkable
biocidal activity as compared to the quaternized silanes which
reach a 99% kill for a time >45 min. The remnant number of
bacterial CFUs after the kill kinetic assay are shown in FIG.
18.
[0336] Antimicrobial tests were also performed on the filled PDMS
sample modified with 1 wt % of the QAM. Biocidal activity of the 1
wt % modified PDMS sample decreased on adding filler (10 wt % FSN,
fumed silica nanoparticles) (FIG. 16). The percent kill ranges from
78% (PA) to 81% (EC), which is .about.20% less than the unfilled
sample and there was a decrease in the log reduction by a factor of
3 (FIG. 19). It is believed that a condensation reaction occurs
between the hydroxyl moieties at the surface of silica
nanoparticles and the methoxy functional groups present in the QAM.
This leads to FSN surface modification and subsequent
internalization of the quaternary charge, rendering the surface
with a lesser concentration of cationic charge. Silica
nanoparticles may be treated with hexamethyldisilazane to
incorporate a trimethylsilyl group at the surface, facilitating
good particle dispersion. Although, in the process of silylation, a
certain fraction of nanoparticle surface may remain unmodified.
[0337] From the present result it is believed that for PR-1 (filled
PDMS), a condensation reaction takes place at the surface of the
nanoparticle between fractions of remnant hydroxyl groups and the
methoxy groups of the modifier. Immobilization of the modifier at
the nanoparticle surface leads to internalization and their
concentration at the surface of the coating would diminish.
[0338] Mechanical property. Polydimethylsiloxane elastomers are
well known for their low glass transition temperatures
(T.sub.g.about.-120.degree. C.) and high thermal stability
(.about.250.degree. C.). Fumed silica nanoparticles (FSN) treated
with hexamethyldisilazane were used as filler for the present
study.
[0339] Tensile tests were done on an unfilled PDMS sample with 1 wt
% of the QAM was (control) and a sample filled with 10 wt % of the
treated FSN. The unfilled sample had a tensile behavior similar to
a PDMS elastomer, with a maximum elongation of 45% at break. The
filled sample underwent 250% elongation before break (FIG. 20).
[0340] Conclusion.
[0341] The present study has shown a new route for synthesizing
thermosetting siloxane-based elastomers having antimicrobial
activity. Small amounts (0.5, 1 and 2 wt %) of a surface modifier
has been added to a PDMS matrix, following a condensation reaction
to concentrate positive quaternary charges at the coating surface.
Streaming potential (SP), an effective engineering technique has
been utilized in this study to quantify the surface accessible
quaternary charge in the modified coatings. Streaming potential
measurements have shown a modifier concentration dependant charge
density, with the SP increasing from P-0 (unmodified control) to
P-2. Antimicrobial assays have demonstrated remarkable biocidal
activity for the P-1 and P-2 coatings against strains of S. aureus,
P. aeruginosa and E. coli, achieving >99% kill in 30 min.
Kinetics of kill was investigated for the P-1 coatings, where they
were observed to affect >99% kill in the first 15 min. Weak
mechanical property of PDMS led to reinforcing a representative P-1
coating with 10 wt % of treated fumed silica nanoparticles. An
improvement in tensile property was observed with an increase in
elongation at break from 45% (P-1) to 250% (PR-1). Adsorption of
the modifier at the nanoparticle surface led to internalization and
a decrease in surface potential and biocidal activity.
Biocompatibility of PDMS combined with antimicrobial activity would
offer immense potential for their use in biomedical
applications.
Example 6
Synthesis and Characterization of DAPMDS-PDMS-PS
[0342] Materials
[0343] 1,3-Propanesultone (1,3-PS) was purchase from Sigma Aldrich.
Dibutyltindiacetate (DBTDA),
N,N-Dimethyl-3-aminopropylmethyldimethoxysilane (DAPMDS), silanol
terminated polydimethylsiloxane (HO-PDMS-OH),
1,2-bis(triethoxysilyl)ethane (BTSE), tetrahydrofuran (THF) were
purchased from Gelest and used without further purification. The
microslides (25.times.75 mm, 1.0 mm thickness) used in this work
were purchased from VWR.
[0344] Synthesis of DAPMDS-PDMS-PS
[0345] The synthetic route of DAPMDS-PDMS is presented in FIG. 21.
N,N-Dimethyl-3-aminopropylmethyldimethoxysilane (0.01 mol) and
silanol terminated PDMS (MW=500-700; viscosity=25 cSt; 0.02 mol)
were added to a 100 mL round bottomed flask in the presence of 0.5%
catalyst, DBTDA, and stirred under nitrogen atmosphere overnight at
room temperature. The DAPMDS contains methoxide groups which easily
hydrolyze to silanol groups, thereafter condensing with the silanol
groups on the PDMS (25 cSt). At the end of the reaction, methanol
formed during the reaction was removed under vacuum and the
intermediate compound DAPMDS-PDMS was obtained.
[0346] The synthetic route of DAPMDS-PDMS-PS, modifier, is
presented in FIG. 22. 1,3-propane sultone (0.01 mol, 1,3-PS,
dissolved in .about.5 mL THF) was added to the stirred reaction
intermediate from step 1 and left to reflux at 50.degree. C.
overnight. THF was removed by rotary evaporation followed by
thorough removal of residual solvent under vacuum.
[0347] Preparation of Coating Finished with Modifier,
DAPMDS-PDMS-PS
[0348] DAPMDS-PDMS-PS (2.0 wt %) and silanol terminated PDMS (1,000
cSt) were introduced into a speed-mixer vial in the presence of 25
L DBTDA, and speed-mixed for a cycle of 60 sec at 2700 rpm. At the
end of the cycle, 0.5 wt % BTESE, cross-linker, was added into the
vial then speed-mixed under the same mixing condition. Under cure
conditions, the silanol groups on the modifier, HO-PDMS-OH and
BTESE co-condense. The surface concentration of DAPMDS-PDMS-PS
imparts antimicrobial activity to the coating. Control samples were
prepared following a similar procedure except without the addition
of modifier.
[0349] Application of Coating on Glass Slides
[0350] The finished resin was swiftly applied to glass slides to
prevent premature curing while ensuring an even distribution over
the surface. Any air bubbles formed during the drip-coating process
were eliminated. When drip-coating was over, the glass slides were
transferred into the oven at 80.degree. C. for 24-48 h. A similar
procedure was followed for the control samples. When the curing was
done, the antimicrobial activity of the coating was assessed.
[0351] Results and Discussion
[0352] .sup.1H NMR Analysis
[0353] NMR spectra was observed for the starting materials (DAPMDS
and PDMS-25 cSt) through the synthesis of the intermediate
compound, DAPMDS-PDMS and confirmed the reaction between the two
starting materials and the formation of modifier,
DAPMDS-PDMS-PS.
[0354] Antimicrobial Properties of Coating
[0355] The antimicrobial activities of coating finished with
modifier were evaluated. The coating without the modifier was
employed as a control. Bacterial colonies were allowed to grow on
the surface of the coating on the glass slides. The antimicrobial
activity was assessed according to their antimicrobial rate. FIG.
23 shows the antimicrobial activity of coating against P. aureus in
parallel with the control. The results show a marked decrease in
the bacterial viable colonies after 30 min contact of a sprayed on
bacterial challenge. Up to 94% kill was found for P. aureus.
[0356] The entire contents of each of U.S. Provisional Application
Ser. Nos. 61/457,977, filed Jul. 26, 2011; and 61/487,991, filed
May 19, 2011; and International Application No. PCT/US12/48425,
filed Jul. 26, 2012 are hereby incorporated by reference.
[0357] This application is based on and claims priority to U.S.
Provisional Application Ser. Nos. 61/552,452, filed Oct. 27, 2011,
and 61/552,454, filed Oct. 27, 2011, the entire contents of each of
which are hereby incorporated by reference.
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