U.S. patent application number 12/397760 was filed with the patent office on 2010-06-03 for antimicrobial compositions.
This patent application is currently assigned to BECTON, DICKINSON AND COMPANY. Invention is credited to David Tien-Tung Ou-Yang.
Application Number | 20100135949 12/397760 |
Document ID | / |
Family ID | 42223012 |
Filed Date | 2010-06-03 |
United States Patent
Application |
20100135949 |
Kind Code |
A1 |
Ou-Yang; David Tien-Tung |
June 3, 2010 |
ANTIMICROBIAL COMPOSITIONS
Abstract
Antimicrobial compositions and methods are disclosed. The
antimicrobial compositions are particularly useful in providing
antimicrobial capability to a wide-range of medical devices. In one
aspect the invention relates a UV curable antimicrobial coating
comprising a UV curable composition comprising an oligomer, a
momoner, and a photoinitiator which are together capable of forming
a UV curable polymer composition. The compositions include rheology
modifiers as necessary. The compositions also include antimicrobial
agents, which may be selected from a wide array of agents.
Representative antimicrobial agents include cetyl pyridium
chloride, cetrimide, alexidine, chlorexidine diacetate,
benzalkonium chloride, and o-phthalaldehyde.
Inventors: |
Ou-Yang; David Tien-Tung;
(Woodbury, MN) |
Correspondence
Address: |
David W. Highet, VP & Chief IP Counsel;Becton, Dickinson and Company
(Kirton & McConkie), 1 Becton Drive, MC 110
Franklin Lakes
NJ
07417-1880
US
|
Assignee: |
BECTON, DICKINSON AND
COMPANY
Franklin Lakes
NJ
|
Family ID: |
42223012 |
Appl. No.: |
12/397760 |
Filed: |
March 4, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61118988 |
Dec 1, 2008 |
|
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|
Current U.S.
Class: |
424/78.17 ;
424/78.08 |
Current CPC
Class: |
C09D 5/1668 20130101;
A61L 2300/208 20130101; C10N 2040/50 20200501; C10M 2201/105
20130101; C10M 2215/06 20130101; C10M 169/04 20130101; C08F 220/18
20130101; C10M 2205/14 20130101; A61L 2300/206 20130101; C09D 4/06
20130101; C08F 222/1006 20130101; C10N 2030/16 20130101; C10M
2215/04 20130101; A61L 29/085 20130101; A61L 29/16 20130101; C10N
2020/06 20130101; B05D 3/0254 20130101; C09D 5/14 20130101; A61L
2300/404 20130101; B05D 3/067 20130101; C10M 2229/0515
20130101 |
Class at
Publication: |
424/78.17 ;
424/78.08 |
International
Class: |
A01N 25/00 20060101
A01N025/00; A01P 1/00 20060101 A01P001/00 |
Claims
1. An antimicrobial ultraviolet (UV) curable coating comprising: a
UV curable composition comprising an oligomer, a momoner, and a
photo initiator; a rheology modifier; and an antimicrobial
agent.
2. The antimicrobial UV curable coating of claim 1 wherein the
oligomer is selected from the group consisting of acrylated
aliphatic urethanes, acrylated aromatic urethanes, acrylated
polyesters, unsaturated polyesters, acrylated polyethers, and
acrylated acrylics.
3. The antimicrobial UV curable coating of claim 2 wherein the
acrylated functional group is selected from the group consisting of
mono-functional, di-functional, tri-functional, tetra-functional,
penta-functional, and hexa-functional acrylates.
4. The antimicrobial UV curable coating of claim 1 wherein the
monomer is selected from the group consisting of 2-ethyl hexyl
acrylate, isooctyl acrylate, isobornylacrylate, 1,6-hexanediol
diacrylate, diethylene glycol diacrylate, triethylene glycol
diacrylate, pentaerythritol tetra acrylate, penta erythritol tri
acrylate, dimethoxy phenyl acetophenone hexyl methyl acrylate, and
1,6 hexanidiol methacrylate,
5. The antimicrobial UV curable coating of claim 1 wherein the
photoinitiator is selected from the group consisting of benzoin
ethers, acetophenones, benzoyl oximes, acyl phosphine oxide, and
Michler's ketone, thioxanthone, anthroguionone, benzophenone,
methyl diethanol amine, and
2-N-butoxyethyl-4-(dimethylamino)benzoate.
6. The antimicrobial UV curable coating of claim 1 wherein the
rheological modifier is selected from the group consisting of
organic clay, castor wax, polyamide wax, polyurethane, and fumed
silica.
7. The antimicrobial UV curable coating of claim 1 wherein the
Theological modifier is fumed silica.
8. The antimicrobial UV curable coating of claim 1 wherein the
antimicrobial agent is selected from the group consisting of
aldehydes, anilides, biguanides, silver, silver compound,
bis-phenols, and quaternary ammonium compounds.
9. The antimicrobial UV coating of claim 1 wherein the
antimicrobial agent is selected from the group consisting of
cetrimide and cetyl pyridium chloride.
10. The antimicrobial UV coating of claim 1 wherein the
antimicrobial agent is selected from the group consisting of
chlorhexidine diacetate, alexidine, and benzalkonium chloride.
11. The antimicrobial UV curable coating of claim 1 wherein the
composition comprises rheological modifier in the amount of from
about 0.1 to about 30 parts by weight in 100 parts by weight the
UV-curable composition.
12. The antimicrobial UV curable coating of claim 1 wherein the
composition comprises Theological modifier in the amount of from
about 0.2 to about 20 parts by weight in 100 parts by the weight of
the UV-curable composition.
13. The antimicrobial UV curable coating of claim 1 wherein the
composition comprises rheological modifier in the amount of from
about 0.2 to about 10 parts by weight in 100 parts by weight of the
UV-curable composition.
14. The antimicrobial UV curable coating of claim 1 wherein the
composition comprises antimicrobial agent in the amount of from
about 0.5 to about 50 parts by weight in 100 parts by weight of the
UV-curable composition.
15. The antimicrobial UV curable coating of claim 1 wherein the
composition comprises antimicrobial agent in the amount of from
about 0.5 to about 30 parts by weight in 100 parts by weight of the
UV-curable composition.
16. The antimicrobial UV curable coating of claim 1 wherein the
composition comprises antimicrobial agent in the amount of from
about 0.5 to about 20 parts by weight in 100 parts by weight of the
UV-curable composition.
17. A UV curable coating composition comprising: a) a UV curable
composition, having; from about 10% to about 90% by weight oligomer
selected from the group consisting of acrylated aliphatic
urethanes, acrylated aromatic urethanes, acrylated polyesters,
unsaturated polyesters, acrylated polyethers, and acrylated
acrylics; from about 5% to about 90% by weight monomer selected
from the group consisting of 2-ethyl hexyl acrylate, isooctyl
acrylate, isobornylacrylate, 1,6-hexanediol diacrylate, diethylene
glycol diacrylate, triethylene glycol diacrylate, pentaerythritol
tetra acrylate, penta erythritol tri acrylate, dimethoxy phenyl
acetophenone hexyl methyl acrylate, and 1,6 hexanidiol
methacrylate; b) from about 0.1 to about 30 parts by weight
rheology modifier in 100 parts UV curable composition, the rheology
modifier selected from the group consisting of organic clay, castor
wax, polyamide wax, polyurethane, and fumed silica; c) from about
0.5 to about 50 parts by weight antimicrobial agent in 100 parts UV
curable composition, the antimicrobial agent selected from the
group consisting of aldehydes, anilides, biguanides, silver, silver
compound, bis-phenols, and quaternary ammonium compounds; and d)
from about 1 to about 10 parts photoinitiator.
18. An antimicrobial coating comprising: a UV curable composition
having an oligomer, a monomer, a photoinitiator, a rheology
modifier; and an antimicrobial agent selected from the group
consisting of cetrimide, cetyl pyridium chloride, chlorhexidine
diactetate, alexidine, and benzalkonium chloride.
19. The antimicrobial coating of claim 17 wherein the antimicrobial
agent is alexidine.
20. The antimicrobial coating of claim 17 wherein the antimicrobial
agent is cetrimide and cetyl pyridium chloride.
21. The antimicrobial coating of claim 17 wherein the antimicrobial
agent is chlorhexidine diacetate.
22. The antimicrobial coating of claim 17 wherein the antimicrobial
agent is benzalkonium chloride.
23. The antimicrobial coating of claim 17 further comprising a
rheology modifier comprising fumed silica.
Description
RELATED APPLICATIONS
[0001] This application claims priority to U.S. provisional patent
application No. 61/118,988, filed Dec. 1, 2008, entitled
"Antimicrobial Compositions and Methods for Medical Product Use,"
which application is incorporated herein by this reference.
BACKGROUND OF THE INVENTION
[0002] The present invention relates to antimicrobial compositions
and methods for use of those compositions in various medical
applications. One of the major challenges of modern medical
treatment is control of infection and the spread of microbial
organisms.
[0003] One area where this challenge is constantly presented is in
infusion therapy of various types. Infusion therapy is one of the
most common health care procedures. Hospitalized, home care, and
other patients receive fluids, pharmaceuticals, and blood products
via a vascular access device inserted into the vascular system.
Infusion therapy may be used to treat an infection, provide
anesthesia or analgesia, provide nutritional support, treat
cancerous growths, maintain blood pressure and heart rhythm, or
many other clinically significant uses.
[0004] Infusion therapy is facilitated by a vascular access device.
The vascular access device may access a patient's peripheral or
central vasculature. The vascular access device may be indwelling
for short term (days), moderate term (weeks), or long term (months
to years). The vascular access device may be used for continuous
infusion therapy or for intermittent therapy.
[0005] A common vascular access device is a plastic catheter that
is inserted into a patient's vein. The catheter length may vary
from a few centimeters for peripheral access, to many centimeters
for central access and may included devices such as peripherally
inserted central catheters (PICC). The catheter may be inserted
transcutaneously or may be surgically implanted beneath the
patient's skin. The catheter, or any other vascular access device
attached thereto, may have a single lumen or multiple lumens for
infusion of many fluids simultaneously.
[0006] The vascular access device commonly includes a Luer adapter
to which other medical devices may be attached. For example, an
administration set may be attached to a vascular access device at
one end and an intravenous (IV) bag at the other. The
administration set is a fluid conduit for the continuous infusion
of fluids and pharmaceuticals. Commonly, an IV access device is a
vascular access device that may be attached to another vascular
access device, closes the vascular access device, and allows for
intermittent infusion or injection of fluids and pharmaceuticals.
An IV access device may include a housing and a septum for closing
the system. The septum may be opened with a blunt cannula or a male
Luer of a medical device.
[0007] When the septum of a vascular access device fails to operate
properly or has inadequate design features, certain complications
may occur. Complications associated with infusion therapy may cause
significant morbidity and even mortality. One significant
complication is catheter related blood stream infection (CRBSI). An
estimate of 250,000-400,000 cases of central venous catheter (CVC)
associated BSIs occur annually in US hospitals. Attributable
mortality is an estimated 12%-25% for each infection and a cost to
the health care system of $25,000-$56,000 per episode.
[0008] A vascular access device may serve as a nidus of infection,
resulting in a disseminated BSI (blood stream infection). This may
be caused by failure to regularly flush the device, a non-sterile
insertion technique, or by pathogens that enter the fluid flow path
through either end of the path subsequent to catheter insertion.
When a vascular access device is contaminated, pathogens adhere to
the vascular access device, colonize, and form a biofilm. The
biofilm is resistant to most biocidal agents and provides a
replenishing source for pathogens to enter a patient's bloodstream
and cause a BSI. Thus, devices with antimicrobial properties are
needed.
[0009] One approach to preventing biofilm formation and patient
infection is to provide an antimicrobial coating on various medical
devices and components. Many medical devices are made with either
metallic or polymeric materials. These materials usually have a
high coefficient of friction. A low molecular weight material or
liquid with a low coefficient of friction is usually compounded
into the bulk of the materials or coated onto the surface of the
substrates to help the functionality of the devices.
[0010] Over the last 35 years, it has been common practice to use a
thermoplastic polyurethane solution as the carrier for
antimicrobial coatings. The solvent is usually tetrahydrofuran
(THF), dimethylformamide (DMF), or a blend of both. Because THF can
be oxidized very quickly and tends to be very explosive, an
expensive explosion-proof coating facility is necessary. These
harsh solvents also attack many of the polymeric materials commonly
used, including polyurethane, silicone, polyisoprene, butyl rubber
polycarbonate, rigid polyurethane, rigid polyvinyl chloride,
acrylics, and styrene-butadiene rubber (SBR). Therefore, medical
devices made with these materials can become distorted over time
and/or form microcracks on their surfaces. Another issue with this
type of coating is that it takes almost 24 hours for the solvent to
be completely heat evaporated. Accordingly, conventional technology
has persistent problems with processing, performance, and cost.
[0011] Another limitation is the availability of suitable
antimicrobial agents for use in such coatings. One of the most
commonly used antimicrobial agents used in coating medical device
is silver. Silver salts and silver element are well known
antimicrobial agents in both the medical surgical industry and
general industries. They are usually incorporated into the
polymeric bulk material or coated onto the surface of the medical
devices by plasma, heat evaporation, electroplating, or by
conventional solvent coating technologies. These technologies are
tedious, expensive, and not environmentally friendly.
[0012] In addition, the performance of silver coated medical
devices is mediocre at best. For example, it can take up to eight
(8) hours before the silver ion, ionized from the silver salts or
silver element, to reach efficacy as an antimicrobial agent. As a
result, substantial microbial activity can occur prior to the
silver coating even becoming effective. Furthermore, the silver
compound or silver element has an unpleasant color, from dark amber
to black.
[0013] Accordingly, there is a need in the art for improved
compositions for providing antimicrobial capability to medical
devices of various types, and particularly devices related to
infusion therapy. Specifically, there is a need for an effective
antimicrobial coating that can be easily applied to medical devices
constructed of polymeric materials and metals. There is also a need
for improved methods of applying such antimicrobial coatings to
medical devices.
BRIEF SUMMARY OF THE INVENTION
[0014] The present invention has been developed in response to
problems and needs in the art that have not yet been fully resolved
by currently available antimicrobial compositions and methods.
Thus, these compositions and methods are developed to reduce
complications, such as the risk and occurrence of CRBSIs, by
providing improved antimicrobial compositions and methods for use
in conjunction with medical devices.
[0015] The present invention relates to ultraviolet (UV)
(wavelength of approximately 200 nm to 600 nm)-curable coatings
that have antimicrobial properties. The coatings may be cured by
light in the range set forth above, namely from about 200 nm to
about 600 nm. In some embodiments, it may be preferable to cure the
composition with light in the range of from about 300 nm to about
450 nm. These coatings are particularly adaptable for use on
medical devices, particularly intravascular access devices like
needleless valves. As mentioned above, the medical devices are
often comprised of polymeric substrates, especially polycarbonate
(PC), polyurethane (PU), polyvinyl chloride (PVC),
styrene-butadiene rubber (SBR), and acrylics.
[0016] In one aspect of the invention the surfaces of such devices
are coated with a UV-curable coating (sometimes hereinafter
referred to as "UV coating") which comprises a UV curable
composition and addition components incorporated therein such as
antimicrobial agents uniformly distributed throughout its matrix.
The antimicrobial agents are able to diffuse through the matrix and
kill microscopic organisms that come in contact with the coating
surface. The antimicrobial agents, which are uniformly distributed
in the UV coating matrix, gradually diffuse out of the matrix when
the matrix is softened by IV fluids. The antimicrobial agents are
then available to kill the microbes that come in contact with the
coating surface.
[0017] The formulations of this invention are generally comprised
of a combination of urethane or polyester-type oligomer with
acrylate-type functional groups, acrylate-type monomers,
photoinitiators, rheological modifiers, and antimicrobial agents.
The nano- or micro-sized particles of the antimicrobial agents are
uniformly and permanently distributed throughout the whole coating
matrix.
[0018] The coatings are solventless and can be sprayed, wiped,
dipped or distributed by using other conventional coating methods
to coat a substrate's surface. They can then be rapidly cured with
ultraviolet light. Curing may be completed in seconds or minutes
depending on the formulation and curing conditions. The coatings of
the present invention are generally efficacious within minutes
instead of hours as with conventional coatings. The coatings also
generally have a pleasant light color or an even clear color.
[0019] A wide variety of oligomers can be used within the scope of
the present invention. It is only necessary that the oligomer be
capable of UV curing and of carrying antimicrobial agents of the
type described herein. For example, the oligomers can be acrylated
aliphatic urethanes, acrylated aromatic urethanes, acrylated
polyesters, unsaturated polyesters, acrylated polyethers, acrylated
acrylics, and the like, or combinations of the above. The acrylated
functional group can be mono-functional, di-functional,
tri-functional, tetra-functional, penta-functional, or
hexa-functional.
[0020] As with the oligomers, a wide range of monomers can be used
in the present compositions. Once again, it is only necessary that
the overall composition be UV-curable and that the composition be
capable of carrying the antimicrobial agents. For example, the
monomers can be 2-ethyl hexyl acrylate, isooctyl acrylate,
isobornylacrylate, 1,6-hexanediol diacrylate, diethylene glycol
diacrylate, triethylene glycol diacrylate, pentaerythritol tetra
acrylate, penta erythritol tri acrylate, dimethoxy phenyl
acetophenone hexyl methyl acrylate, 1,6 hexanidiol methacrylate,
and the like, or combinations of these compounds.
[0021] In order to allow for UV-curing, the composition should be
provided with an adequate and compatible photoinitiator. In certain
embodiments of the invention, the photoinitiators can be: 1) single
molecule cleavage type, such as benzoin ethers, acetophenones,
benzoyl oximes, and acyl phosphine oxide, and 2) hydrogen
abstraction type, such as Michler's ketone, thioxanthone,
anthroguionone, benzophenone, methyl diethanol amine,
2-N-butoxyethyl-4-(dimethylamino) benzoate, and the like, or
combinations of these materials.
[0022] In certain embodiments, a rheological modifier can
preferrably be added to the composition. The rheological modifier
allows the flow characteristics of the composition to be controlled
and modified as desired. The rheological modifier can also aid in
the uniform distribution of antimicrobial agent and other materials
within the composition. Suitable rheological modifiers may include
organic clay, castor wax, polyamide wax, polyurethane, and fumed
silica or combinations of these materials.
[0023] Various antimicrobial agents may be used in the compositions
of the present invention. It is only necessary that the
antimicrobial agent be compatible with the other components of the
compositions and that it be effective in controlling microbial
agents. Specifically, it is preferred that that antimicrobial agent
not chemically react with the other components of the composition.
As discussed above, in certain embodiments it is preferred that the
antimicrobial agent be capable of moving within the matrix of the
composition such that it can be delivered to the site of the
microbial agent. Examples of suitable antimicrobial agents within
the scope of the present invention include be aldehydes, anilides,
biguanides, silver element or its compounds, bis-phenols, and
quaternary ammonium compounds and the like or combinations of the
above.
[0024] In another aspect, the invention may be solventless. As
mentioned above, many conventional coatings employ harsh solvents
such as THF and DMF. The present invention is operable without the
use of solvents and, therefore, avoids the difficulties presented
by the use of conventional solvents.
[0025] The formulations also demonstrate good adhesion to numerous
plastic surfaces (such as PC, PU, PVC, acrylics, and SBR). The
formulation can be cured with adequate ultraviolet light
(wavelength of approximately 200 nm to 600 nm, and in certain
embodiments in the range of from about 300 nm to about 450 nm).
[0026] Accordingly, the present invention provides antimicrobial
coating compositions which overcome many of the limitations of
existing technology. The present invention employs known components
which have achieved acceptance for medical use. These components
are combined and used easily and efficiently. As set forth above,
the compositions of the present invention generally including
oligomers, monomers, photoinitiators, rheological modifiers, and
suitable antimicrobial agents. The resulting compositions are
easily applied to the surfaces of medical devices and quickly cured
by UV light.
DETAILED DESCRIPTION OF THE INVENTION
[0027] This detailed description of the invention provides
additional description of each of the aspects of the invention
summarized above. In one aspect of the invention, an antimicrobial
ultra violet (UV)-curable coating is provided. The coating
comprising a UV curable composition comprising an oligomer, a
monomer, and a photoinitiator which are together capable of forming
a UV curable polymer composition. In certain embodiments, the
composition may also include a rheology modifier in order to
improve the flow characteristics of the composition and uniform
distribution of components within the compositions. Finally,
incorporated within the UV curable coating compositions is an
effective antimicrobial agent.
[0028] The UV curable coating compositions are comprised primarily
of one or more oligomers and one or more monomers, combined with
one or more suitable photoinitiators. In following discussing, the
UV curable coating composition will comprise 100 parts by weight.
Materials added to the UV curable coating composition may include
rheological modifiers, antimicrobial agents, and other additives.
These materials will be defined in parts by weight added to 100
parts by weight of the UV curable coating composition.
[0029] The oligomer is generally selected from the group consisting
of acrylated aliphatic urethanes, acrylated aromatic urethanes,
acrylated polyesters, unsaturated polyesters, acrylated polyethers,
acrylated acrylics, and the like, or combinations thereof. The
acrylated functional group is selected from the group consisting of
mono-functional, di-functional, tri-functional, tetra-functional,
penta-functional, and hexa-functional acrylates. Any oligomer which
is compatible with the other components of the composition is
usable within the scope of the present invention. The oligomer will
typically comprise from about 10% to about 90% of the UV curable
composition. In some embodiments the oligomer will comprise from
about 20% to about 80% of the UV curable composition. In certain
embodiments of the invention the oligomer will comprise from about
30% to about 70% of the UV curable composition.
[0030] The monomer is selected from the group consisting of 2-ethyl
hexyl acrylate, isooctyl acrylate, isobornylacrylate,
1,6-hexanediol diacrylate, diethylene glycol diacrylate,
triethylene glycol diacrylate, pentaerythritol tetra acrylate,
penta erythritol tri acrylate, dimethoxy phenyl acetophenone hexyl
methyl acrylate, 1,6 hexanidiol methacrylate and the like, or
combinations of these compounds. Once again any monomer which is
compatible with the other components of the composition is usable
within the scope of the present invention. The monomer will
typically comprise from about 5% to about 90% of the UV curable
composition. In some embodiments the monomer will comprise from
about 10% to about 75% of the UV curable composition. In certain
embodiments of the invention the monomer will comprise from about
20% to about 60% of the UV curable composition.
[0031] The photoinitiator is selected from the group consisting of
single molecule cleavage type, such as benzoin ethers,
acetophenones, benzoyl oximes, and acyl phosphine oxide, and
hydrogen abstraction types consisting of Michler's ketone,
thioxanthone, anthroguionone, benzophenone, methyl diethanol amine,
and 2-N-butoxyethyl-4-(dimethylamino) benzoate. The photoinitiaor
will also be selected such that it is compatible with the other
components of the composition is usable within the scope of the
present invention. The photoinitiator will typically comprise from
about 0.5% to about 10% of the UV curable composition. In some
embodiments the photoinitiator will comprise from about 1% to about
8.5% of the UV curable composition. In certain embodiments of the
invention the photoinitiator will comprise from about 2% to about
7% of the UV curable composition.
[0032] As mentioned above, certain additional components are added
to the UV curable composition. Prominent among these are suitable
rheological modifiers and antimicrobial agents. As mentioned above,
the amounts of these additional components will be expressed in
parts by weight added to 100 parts by weight of UV-curable
composition.
[0033] The rheological modifier is selected from the group
consisting of organic clay, castor wax, polyamide wax,
polyurethane, and fumed silica. The Theological modifier generally
comprises from about 0.1 to about 30 parts by weight added to 100
parts by weight of UV curable composition, i.e. the UV curable
composition is 100 weight units, while the rheological modifier
comprises from about 0.1 to about 30 parts of additional weight. In
other embodiments, the rheological modifier comprises from 0.1 to
about 20 parts by weight compared to 100 parts by weight of the UV
curable composition. In certain further embodiments, the
Theological modifier comprises from about 0.2 to about 10 parts by
weight compared to 100 parts by weight of the UV curable
composition.
[0034] The antimicrobial agent is generally selected from the group
consisting of aldehydes, anilides, biguanides, silver, silver
compound, bis-phenols, and quaternary ammonium compounds. The
antimicrobial agent is generally present in the amount of from
about 0.5 to about 50 parts by weight in compared to 100 parts by
weight of the UV curable composition. In other embodiments, the
antimicrobial agent may be present in the amount of from about 0.5
to about 30 parts by weight of the composition. In certain further
embodiments, the antimicrobial agent is present in the amount of
from about 0.5 to about 20 parts by weight.
[0035] The antimicrobial agent may either dissolve in the UV
curable composition or may be uniformly distributed therein. In
this manner it is found that sufficient antimicrobial agent can
migrate within the composition to contact the location of microbial
activity. In any event, it is preferred that the antimicrobial
agent not react chemically with the other components of the
compositions.
[0036] The UV coating formulations can be urethane or polyester
type arylate such as 7104, 7101, 7124-K, 7105-5K from Electronic
Materials Inc. (EMI) (EM Breckenridge, Co.), 1168-M, I-20781 from
Dymax Corporation (Torrington, Conn.), UV 630 from Permabond
Engineering Adhesives (Somerset, N.J.). The viscosity of the
coating should be less than 10,000 cps, preferable below 5,000 cps,
and most preferably between 20 to 1,000 cps.
EXAMPLES
Example 1
[0037] UV-curable compositions within the scope of the present
invention were formulated and their microbial kill rate and zone of
inhibition were tested as set forth in Table 1 below. Each of the
compositions was essentially identical except for the antimicrobial
agent which was varied as set forth below. The composition was
comprised of a UV curable composition designated EMI 7104. The UV
curable composition was comprised of 30-70% oligomer, 20-60%
monomer; 2-7% photoinitiator. Added to 100 parts of the UV curable
composition was 2.6 parts fumed silica obtained from Cabot and
designated Cabot's MS-55. Also added was 7.2 parts antimicrobial
agent. The specific antimicrobial agent was used in the formulation
were as follows: [0038] Samples #1. Chlorhexidine diacetate [0039]
2. Alexidine [0040] 3. Silver sulfadiazine [0041] 4. Silver acetate
[0042] 5. Silver citrate hydrate [0043] 6. Cetrimide [0044] 7.
Cetyl pyridium chloride [0045] 8. Benzalknonium chloride [0046] 9.
o-phthalaldehyde [0047] 10. Silver element
[0048] Each composition was tested on three (3) microbial agents,
namely: Staphylococcus epidermidis (gram positive bacteria),
Pseudomonas aeruginosa (gram negative bacteria), and Candida
albicans (yeast or fungi). The results are summarized in Table
1.
TABLE-US-00001 TABLE 1 The Contact Kill and Zone of Inhibition of
UV Coating.sup.1 Formulations Contact Kill (% Kill) Zone of S.
epidermidis.sup.3 P. aeruginosa C. albicans Inhibition (mm) Sample
#.sup.2 1 min 1 hr 8 hr 1 min 1 hr 8 hr 1 min 1 hr 8 hr S. epider
P. aerug C. albican 1 74.4 100 ND 90.6 100 ND growth 100 ND 22.5
13.5 23.0 2 79.3 100 ND 71.4 100 ND growth 100 ND 13.5 0.0 13.5 3
0.0 35.5 100 44.3 85.5 100 growth growth 100 14.0 13.5 18.0 4 4.6
32.2 100 20.0 29.8 100 growth growth growth 13.0 12.0 15.0 5 11.5
31.4 100 37.1 36.2 100 growth growth 100 7.0 6.5 9.0 6 100 ND ND
100 ND ND 100 ND ND 28.5 7.5 24.0 7 100 ND ND 100 ND ND 100 ND ND
18.0 0.0 15.0 8 20.7 ND 100 100 ND ND growth 100 ND 21.5 0.0 22.5 9
2.3 20.3 100 7.1 0.0 100 growth growth 100 0.0 0.0 0.0 10 1.2 44.1
100 24.3 46.8 100 growth growth growth 105 9.0 12.0 ND - no data in
view of 100% kill previously Growth - continued microbial
growth
[0049] Each of the compositions was generally effective in killing
the bacterial agents. All of the compositions, except that
containing silver element, were effective in killing Candida
albicans with one (1) hour. As set forth in Table 1 is appears that
cetyl pyridium chloride and cetrimide were generally more effective
than the other antimicrobial agents.
Example 2
[0050] In these examples several antimicrobial agents were
incorporated into UV curable coating compositions within the scope
of the present invention. Each of the formulations included 100
parts of 7104 UV coating, 2.6 parts of fumed silica [designed M-5],
and 5.0 parts of antimicrobial agent. Silver and chlorhexidine were
included in the test because they are commonly used antimicrobial
agents being used in medical technologies. The results of these
tests are set forth in Table 2.
TABLE-US-00002 TABLE 2 Contact Kill and Zone of inhibition of
selective antimicrobial agents in UV formulation (5% agents)
Products Contact Kill (%) Zone of Inhibition 1 Minute (5%) S. Epi
P. Aeru C. Albi S. Epi P. Aeru C. Albi Chlorhexidine 37.6 0.0 39.0
21.5 13.5 19.0 Diacetate Cetrimide 72.2 96.6 87.8 30.0 0.0 23.0
Cetyl Pyridium 100.0 100.0 100.0 16.5 0.0 13.0 Chloride
Benzalkonium 15.8 0.0 58.5 23.5 0.0 23.5 Chloride Silver*.sup.2 --
-- -- -- -- -- Chlorhexidine -- -- -- -- -- -- Gluconate*.sup.2
[0051] When 7 parts antimicrobial agent is used the results set
forth in Table 3 were obtained.
TABLE-US-00003 TABLE 3 Contact Kill (%) and Zone of inhibition (mm)
of selective antimicrobial agents in UV formulation (7% agents)
Products Contact Kill (%) Zone of Inhibition 1 Minute (7%) S. Epi
P. Aeru C. Albi S. Epi P. Aeru C. Albi Chlorhexidine 24.6 37.7 26.3
21.8 11.5 17.3 Diacetate Cetrimide 100 100 97.3 28.5 "+" 20.5 Cetyl
Pyridium 100 100 100 16.3 0.0 13.0 Chloride Benzalkonium 100 100
72.9 24.8 0.0 23.5 Chloride Silver 0.0 0.0 13.7 7.5 7.5 10.0
Chlorhexidine 0.0 0.0 2.0 13.0 0.0 0.0 Gluconate
Example 3
[0052] In Table 4, the formulation set forth above was prepared
using cetyl pyridium chloride (formulation #1) as the antimicrobial
agent. This composition has 100% contact kill within 1 min. The
same formulation using chlorhexidine diacetate (formulation #4) as
the agent has 100% contact kill within 1 hour for all three types
of microorganisms. However, both conventional compositions had 100%
contact kill for selected microbes only after about 8 hours (both
are using silver compound or silver element as the agent).
TABLE-US-00004 TABLE 4 Commercial Formulation Analysis Contact Kill
(%) Zone of Inhibition (mm) Products S. Epi P. Aeru C. Albi S. Epi
P. Aeru C. Albi Commercial Formulation 1 1 min. -- -- -- -- -- -- 1
hr. 0.0 9.2 11.0 8 hr. 100 99.7 0.0 Commercial Formulation 2 1 min.
0.0 0.0 13.7 7.5 7.5 10.0 1 hr. 0.0 100 95.2 8 hr. 100 100 89.5
(PC) 1 1 min. 100 100 100 16.3 0.0 13.5 1 hr. 100 100 100 8 hr. 100
100 100 (PC) 4 1 min. 24.6 37.7 26.3 21.8 11.5 17.3 1 hr. 100 100
100 8 hr. 100 100 100 (PC) 1: Cetyl pyridium chloride as the agent.
(PC) 4: Chlorhexidine diacetate as the agent
Example 4
[0053] Table 5 shows that the four agents identified above can have
100% contact kill within 1 hour and last up to almost 4 days when
using S. epidermidis as the microbe. However, conventional silver
agent formulations have no 1 hour contact kill at all starting from
day 1.
TABLE-US-00005 TABLE 5 Saline Leach Rate Tests for Selected
Antimicrobial Agents (1 hr. contact kill by using Staphylococcus
epidermidis as the microbe) 0 Hr 24 Hrs 48 Hrs 72 Hrs 94 Hrs 1 100
100 100 100 100 2 100 100 100 100 100 3 100 100 100 100 100 4 100
100 100 100 100 5 0.0 1.96 0.0 0.0 0.0 6 100 76.5 55.4 87.8 100 *
Note: 1. Cetyl pyridium chloride 2. Cetrimide 3. Benzalkonium
chloride 4. Chlorhexidine diacetate 5. Silver 6. Chlorhexicine
gluconate
Example 5
[0054] Saline leach tests were conducted on the compositions
described above. As set forth in Table 6 it was observed that
chlorhexicine gluconate significantly loses its 1 hour contact kill
ability after 48 hours when using P. aeruginosa as the microbe.
However, the other agents appear to retain contact kill ability for
up to 94 hours.
TABLE-US-00006 TABLE 6 Saline Leach Rate Tests for Selected
Antimicrobial Agents (1 hr. contact kill by using Pseudomonas
aeruginosa as the microbe) 0 Hr 24 Hrs 48 Hrs 72 Hrs 94 Hrs 1 100
100 100 100 100 2 100 100 100 100 100 3 100 100 100 100 99.4 4 100
100 100 100 100 5 100 100 100 100 100 6 100 96.0 96.5 1.2 0.0 *
Note: 1. Cetyl pyridium chloride 2. Cetrimide 3. Benzalkonium
chloride 4. Chlorhexidine diacetate 5. Silver 6. Chlorhexicine
gluconate
Example 6
[0055] From the data in Table 7, it is clear that both conventional
formulations (silver or chlorhexidine gluconate) significantly lose
their efficacy after 24 hours when using Candida albicans as the
microbe. The top four agents tested herein have 100% efficacy for
up to 94 hrs.
TABLE-US-00007 TABLE 7 Saline Leach Rate Tests for Selected
Antimicrobial Agents (1 hr. contact kill by using Candida albicans
as the microbe) 0 Hr 24 Hrs 48 Hrs 72 Hrs 94 Hrs 1 100 100 100 100
100 2 100 100 100 100 100 3 100 100 100 100 100 4 100 100 100 100
100 5 95.2 97.6 62.4 30.0 39.7 6 87.6 100 29.1 25.4 12.7 * Note: 7.
Cetyl pyridium chloride 8. Cetrimide 9. Benzalkonium chloride 10.
Chlorhexidine diacetate 11. Silver 12. Chlorhexicine gluconate
Example 7
[0056] In this example several formulations within the scope of the
present invention were made. The UV-curable composition was varied
using various proprietary formulations manufactured by EMI.
Antimicrobial activity was measured and compared to elongation at
break. The data is as follows:
TABLE-US-00008 TABLE 8 Elongation at Break 0 Hour 24 Hour 48 Hour
72 Hour 96 Hour S. epidermidis - 1 Hour 1 100 100 100 100 100 11
100 90.5 10.6 0 0 31 90.7 0 23.4 0 0 41 100 100 100 100 100 51 100
100 100 100 100 P. aeruginosa - 1 Hour 1 100 100 99.8 100 100 11
100 100 0 0 0 31 100 100 0 0 0 41 100 100 98.8 100 100 51 100 0 0 0
0 C. albicans - 1 Hour 1 100 100 91.7 89.7 97.1 11 100 59.6 22.2 0
0 31 50 24.5 8.33 0 0 41 100 100 97.9 95.5 99.6 51 100 73.9 12.5 0
0
* * * * *