Note: Descriptions are shown in the official language in which they were submitted.
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WO 99/05909 ~ PCT/US97/13222
ANTI-BACTERIALIANTI-VIRAL COATINGS,
COATING PROCESS AND PARAMETERS THEREOF
Background of the Invention
The invention relates to a method for coating a substrate with an
anti-pathogenic agent to render the substrate suitable for use as a barrier
against
pathogens. Specifically, the invention provides a method for coating a range
of
substrates with an anti-pathogenic agent such that in the dry state the
substrate
acts as a barrier to block the progress of pathogens and in the wet state the
substrate coating is activated to release the anti-pathogenic agent and
eliminate
pathogens upon contact thereof with the agent. The invention further relates
to
various methods of coating substrates and to the products produced according
to
the methods.
It is well known in the related technology field to incorporate an
anti-bacterial agent into a material or fabric intended for use in medical
applications to guard against the transfer of contagious and potentially
lethal
pathogens. The incorporation of such agents has been accomplished by coating
the outer surface of the material, by interply coating of multi-ply fabric or
material, or by chemically incorporating the coating agent into the material
at
the time of production.
Further, the use of various agents has been reported. For
example, agents have been successfully incorporated into medical-type
materials,
whether paper or polymeric in nature, to guard against the spread of
infection.
Among those agents which have been coated onto or incorporated in paper-based
substrates are bisoxirane compounded with phenolic active agents (U.S. Patent
No. 4,855,139); silicone quaternary amine agents (U.S. Patent No. 4,736,467);
2-amino-4-oxo-tricyclicpyrimidine antiviral agents (U.S. Patent No.
4,625,026);
monocarboxylic acid antimicrobial agents (U.S. Patent No. 4,430,381); and the
' use of polyvinylpyrrolidone-iodine complex as a broad spectrum anti-
microbial
agent (U.S. Patent No. 5,069,907). Similar agents have been used in preparing
materials comprising polymeric compounds that exhibit anti-viral
characteristics.
CA 02301019 2003-02-04
For example, nonoxynol-9 (U. S. Patent No. 5,130,159); organosilicone
quaternary ammonium compounds (U.S. Patent No. 5,126,138); and
biguanide(chlorhexidine) (U. S. Patent No. 4,999,210). It has further
been shown to use nonoxynol-9, a known spermicide, in conjunction
:i with PVP-I complex, a known bactericide, in the high energy
coprecipitate form to protect against the spread of viral and
bacterial infection, including the HIV virus (U.S. Patent No.
5,380,523). Many of the foregoing, however, represent products or
compounds which if used in the manner contemplated herein and fully
disclosed hereinafter would prove irritating to the skin or difficult
to commercially produce. Moreover, the prior attempt at using the
high energy coprecipitate of PvP-I/N-9, while it does achieve the
desired anti-viral result, is of limited commercial value due to
complications i.n manufacture and use of the product disclosed.
1'.i It is, therefore, an object of the subject invention to provide
an anti-pathogenic coating to a medical-type substrate in a
commercially viable manner.
Brief summary of the Invention
The invention generally relates to a method of imparting anti-
pathogenic properties to a substrate material by coating the
substrate with a coating composition containing an anti-pathogenic
agent consisting essentially of PVP-I and N-9 in a ratio of from
about 100:0 to about 0:100 of PVP-I to N-9, the coating composition
further containing a pre-mix solution with which the anti-pathogenic
2.'i agent is intimately mixed in a ratio of from about 6:4 to about 8:2
of agent to pre-mix on a dry basis, and having a percent solids
content of from about 5~ to about 35~ solids. The invention further
relates to the preparation of the coating composition and to the
composition itself.
3() The invention relates to a method of imparting anti-pathogenic
properties to a substrate material wherein said method includes
preparation of an anti-pathogenic coating solution and subsequently
using said coating solution to coat said substrate, said method
comprising (a) preparing a coating composition containing an anti-
3'i pathogenic agent consisting essentially of PVP-I and N-9 in a ratio
of from about 100:0 to about ):100 of PVP-I to N-9, the coating
composition further containing a premix solution with which the anti-
pathogenic agent is intimately mixed in a ratio of from about 6:4 to
2
CA 02301019 2003-02-04
about 8:2 of agent to pre-mix on a dry basis, and having a percent
solids content of from about 5% to about 35% solids, said coating
composition being prepared by (i) preparing a solution of
polyethylene glycol (PEG) in a mixture of alcohol and water; (ii)
:i adding a surfactant comprising a polyethylene glycol sorbitan fatty
acid ester compound and an alcohol/water solution to the PEG solution
with stirring until homogeneously mixed; (iii) adding to the mixture
of step (ii) a prepared powder mixture comprising hydroxypropyl
methylcellulose and hydrous magnesium silicate and stirring to obtain
a homogeneous solution of the power mixture of step (ii); (iv)
stirring the solution of step (iii) for a time sufficient to affect a
homogeneous mixture thereof; and (v) adding with stirring to the
homogeneous solution of step (iv) a pre-prepared solution comprising
a mixture of (1) a solution of PVP-I in an ethanol/water solvent and
1-'i (2) a solution of N-9 in an ethanol/water solvent, the resulting
anti-pathogenic composition exhibiting a viscosity of about 50-
600cps; (b) feeding the anti-pathogenic coating composition into a
coating machine; (c) loading a substrate onto the coating machine;
(d) operating the coating machine such that the coating composition
comes into intimate contact with at least one surface of the
substrate; and (e) drying the coated substrate material.
The invention generally relates to an anti-pathogenic solution
comprising a solution characterized by a % solids of 31.4% and the
inclusion of a solution of PVP-I and N-9 as the active anti-
2.'~ pathogenic agent, the components of the solution being present in a
ratio of from about 100:0 to about 0:100 PVP-I:N-9 and further
including premix solution, wherein on a wet weight basis the anti-
pathogenic agent solution comprises 71.5% by weight active anti-
pathogenic agent and 28.5% by weight premix solution, and further
3(1 wherein the active anti-pathogenic agent comprises 93.3% by weight
PVP-I and 6.7% by weight N-9 and the premix solution comprises 54.6%
by weight polyethylene glycol solution in distilled water and
ethano1,5.4% by weight polyoxyethylene sorbitan monoolete, 11.5% by
weight talc, and 21.3% by weight ethanol solvent or the equivalent
3'~ dry weight for each component consistent with the recited % solids,
the anti-pathogenic solution exhibiting a viscosity between about 90
cps and about 130 cps, the solution substantially completely
eliminating pathogens from a surface upon contact.
2a
CA 02301019 2003-02-04
The invention generally relates to a process for preparing an anti-
pathogenic coating composition for coating paper, plastic, woven and
non-woven substrates and combinations thereof, comprising (a)
preparing a solution of polyethylene glycol (PEG)in a mixture of
S alcohol and water; (b) adding a suffacant comprising a polyethylene
glycol sorbitan fatty acid ester compound and an alcohol/water
solution to the PEG solution with stirring until homogeneously mixed;
(c) adding to the mixture of step (b) a pre-prepared powder mixture
comprising hydroxypropyl methylcellulose and hydrous magnesium
silicate and stirring to obtain a homogenous solution of the powder
mixture of step(b); (d) stirring the solution of step (c) for a time
sufficient to affect a homogenous mixture thereof; and (e) adding
with stirring to the homogenous solution of step (d) a pre-prepared
solution comprising a mixture of (1) a solution of PVP-I in an
ethanol/water solvent and (2) a solution of N-9 in an ethanol/water
solvent, the resulting anti-pathogenic composition having percent
solids of about 25% to about 35% and a viscosity of about 50-600cps.
2b
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WO 99/05909 .
PCT/US97/13222
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, Detailed Description
Statement of Invention
The subject invention relates to a process for producing substrates
coated with a formulation containing a novel anti-pathogenic component. Upon
contact of the coated substrate with a pathogen-containing material, the anti-
pathogenic component is released to eliminate any pathologic affect of the
pathogen. The invention further relates to the preparation of the anti-
pathogenic-containing formulation, to the coating process, and to products or
articles prepared from the coated substrates and their use.
As used herein, the term "coated substrate" refers to any substrate
which ultimately, in finished form, contains the anti-pathogenic component,
whether the component is coated on the surface of the substrate, is imbedded
in
the substrate during substrate production, or is included in the finished
substrate
in another manner, as described hereinafter.
Also, the term "pathogen" and "pathogenic properties" in its
various forms is used herein to mean and include such terms as viral,
bacterial
and HIV. Therefore, reference to an "anti-pathogen" or "anti-pathogenic
property/activity" includes reference to anti-viral, anti-bacterial and/or
anti-HIV
compositions and their anti-viral, anti-bacterial and/or anti-HIV activity.
The
term is used to refer to the use of the subject formulation, coated on an
appropriate substrate, to neutralize or eliminate the undesirable affects of a
pathogen by protecting against contact with the pathogen and further, upon
contact with bodily fluids and/or skin, by eliminating the pathogenic
activity.
BASIC DESIGN
Coating Techniques
For high speed web coating of solvent formulations, common
coating techniques include reverse roll, rod, and gravure coating methods.
Roll
coating methods further include kiss coating, single roll coating, and double
roll
coating, among others. Reverse roll, rod, and gravure coating techniques are
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preferred herein because they offer the ability to put down uniform coatings
at
high speeds, as well as the ability to use formulations with medium to high
solids content, thus minimizing wasted solvent which is volatized in the
drying
process.
The reverse roll coating method is commonly used to apply heavy
to light weights of coatings, but has limited capability for very light weight
coating application, below about 11b./3,000 ft2. In this coating method the
web,
or substrate, travels at surface speed around a first, robber roll while in
contact
with a second steel applicator roll which is rotating at high speed in the
opposite
direction at the point of contact. A third metering roll contacts the
applicator
roll. The coating formulation is transferred from the applicator roll onto the
web. Viscosity, percent solids, and specific gravity of the coating
formulation
affect coating quality and coat weight, as well as mechanical parameters, such
as
the pressure setting between the applicator roll and the rubber roll,
differential
speed of the rollers with respect to each other, and the gap between the
applicator and metering rolls.
Rod coating involves passing the substrate web over an applicator
roll that turns in the liquid coating formulation, transferring an excess of
coating
to the bottom side of the web. The excess is removed by means of a wire of
specific gauge which is wound around a rod positioned behind the applicator
roll. The rod is generally ~/a inch to '/Z inch in diameter, and the wire
gauge
generally runs from 3 gauge up to 32 gauge or higher. The choice of wire
gauge determines the resulting coat weight. Of course, parameters of the
coating formulation, i.e., such as viscosity and total solids, and other
mechanical
parameters also affect coating weight.
Grawre coating, as used herein, operates on the same principles
that the grawre printing method operates on, except that in this instance the
goal
is to achieve 100% coverage of the substrate. Because this method involves the
deposition of coating material in a pattern dictated by the cell pattern
design and
depth on the grawre cylinder, the coating formulation must be sufficiently
fluid
r
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-S-
to flow and transfer to the substrate prior to drying in order to result in a
continuous coating. This method is generally more suitable for the deposition
of
lower coating weights, as compared to reverse roll and rod coating. The amount
of coating used is more accurately metered by this method, making it a viable
option.
One limitation of the foregoing coating techniques is that they
require the use of substantially non-porous substrates. If the substrate is
excessively porous, it becomes difficult to control coat weight and to
properly
track the web through~the coating machine, i.e., the coating may offset onto
the
machine rolls.
For paper and film substrates, this does not generally pose a
problem. Most papers and films have sufficient coating hold-out or, in other
words, are sufficiently non-porous. Occasionally, a paper substrate may be
excessively porous and require an alternate coating technique to be used.
For the reasons just stated, non-woven substrates, the majority of
which tend to be porous, do not lend themselves to conventional solvent
coating
techniques such as reverse roll, rod, or gravure. In these cases, several
alternate approaches to coating the substrate may be taken, for example:
fabric
treatment which enables the coating to be applied; the use of non-woven fabric
laminated to a film or other impervious substrate, which is a viable solution
given the current increase in the use of non-woven laminates in medical
markets
for a variety of reasons; and the use of alternate coating techniques, which
may
require formulation modification.
Suitable alternate coating techniques for use with the subject
invention include spray and dip coating techniques.
Spray coating is highly suited to use for more porous substrates
because it affords greater control over penetration of the coating into the
substrate. With spray coating the coating formulation is essentially atomized
into a fine mist so that it can be applied to the porous substrate without
excess
penetration to the opposite side of the substrate, assuming heavy coat weights
CA 02301019 2000-02-10 ,
WO 99/05909 ~ ~ PCT/US97/13222
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are not applied. However, the spray coating could also be applied to both
sides
of the web, if desirable. In order to atomize the coating formulation, it
should
be thinned. Proper atomization of the coating is important to the even and
uniform application of the coating, as are the amount and pressure of air
flow.
S Disadvantages of the spray coating technique are that atomization generally
requires a formulation having lower solids, therefore wasted solvent and
overspraying may be problems. Further, it can sometimes be difficult to
control
coat weight uniformity when using the spray coating technique.
Dip coating is another viable alternative coating method. Dip
coating is probably the simplest form of coating in terms of equipment,
however
uniformity of coating requires that great care be taken to control the rate of
withdrawal of the substrate from the coating, solvent evaporation, drainage,
etc.
In this technique, the substrate is passed from a lead-in roll to an immersion
roll
placed in or over a coating pan. The immersion roll is positioned high or low
depending on the desire to coat only one or both sides of the paper. This
method, like spray coating, requires low solids content of the coating
formulation and is significantly affected by the porosity of the substrate, as
well
as by environmental and mechanical parameters. In dip coating, the entire non-
woven substrate is immersed in the coating and the substrate is impregnated.
Because a lower solids formulation is typically required, environmental
concerns
due mostly to solvent evaporation must be addressed.
For spray and dip coating, the standard formulation is typically
diluted to generally S-20 % solids, preferably 10 % solids, as compared to a
%-35 % solids range usable with roll coating methods and techniques. In
25 addition, the coating formulation can be modified in other manners
regarding
component content levels to achieve coatable solutions for a given technique.
r
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WO 99/05909 ~ PCT/US97/13222
Substrates Suitable for Use in Conjunction
With the .Anti-Pathogenic Formulation
Suitable substrates for use in conjunction with the anti-pathogenic
formulation described hereinafter include substrates, including but not
limited to,
paper, paper laminates, non-woven materials, non-woven laminates, and other
similar substrates. The invention is primarily concerned with substrates
targeted
for use in medical-type applications, such as surgical gowns and drapes,
examining table paper, hospital bed pads, hospital bed inserts and sheeting,
surgical masks and other hospital or medical-type applications which will be
readily apparent to the skilled artisan after reading and understanding the
technology disclosed herein. The term "medical" as used herein further
includes
the use of the described and similar items in dental and other medically
related
environments, i.e. tray liners and instrument wraps, masks, dental patient
bibs,
etc.
While the primary use of the invention is in the medical-type
environment, it is also envisioned that the coated substrates described will
find
application in personal hygiene type uses, such as toilet seat covers. This
type
of item includes not only publicly provided items, but also personal items
which
can be carried by an individual for private use.
Given the variation in the useful environments for the intended
application of these coated substrates, there is a wide variety of potential
substrate materials.
I. Paper Substrates
One potential substrate is paper, which once coated may be used,
for instance, as examining table roll or cover where there is a high risk of
exposure to bacteria and other viral pathogens. Other uses for coated paper
products include tray liner paper for surgical or medical instrument trays,
wrapping for sterilized surgical or medical instruments, medical packaging
paper, and other uses.
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_g_
For the foregoing and other similar applications, appropriate paper .
substrates include medium weight papers which are not too flimsy, and
therefore
do not easily tear or shred, but which are also not too heavy. The paper must
be able to withstand winding tensions on a web coating machine or apparatus
without suffering performance degradation. Further, papers suitable for this
application should exhibit good hold out, which is closely related to the
porosity
of the substrate and is exhibited by the capability of the paper to maintain
the
coating without penetration or bleed through. Other characteristics which will
affect the suitability of a paper substrate for use in this invention include
the
tensile strength of the paper, the stiffness of the paper, drapeability,
alcohol and
water repellency, bursting strength, air permeability, flammability, and
abrasion
and tear resistance. It is intended that these paper substrates, once coated,
act as
a barrier to bacteria and viruses in the dry state, and become activated,
releasing
the anti-pathogenic component, to eliminate bacteria and viruses when wet.
Specific examples of suitable paper substrates include standard
paper substrates made from wood pulp and processed with cellulosic fibers. For
example, suitable grade paper for the intended processing and uses may be
selected from papers ranging between 17.5 lb. to 20 lb. per 3000 ftZ,
available
currently from James River Corporation under the Flexpac tradename,
specifically BL FLEXPAC 20 TM LG, l7.SfJ to 20.0/I, and even a 13 lb. per
3000 ft2 grade paper available commercially from Coastal Paper Company by
the designation BL MG PR HWS. The preferred grade of paper, then, is
probably in a range between about 10 lb. per 3000 ftz to about 30 Ib. per 3000
ft2, with the selection within this range being dependent upon the intended
use,
i.e., the lighter weights may be suitable examining table paper while the
heavier
weights would be better suited to paper gowns. This range, however, may be
extended beyond the stated limits as long as the paper substrate can meet the
.
criteria stated above for processing and use, mechanically as well as with
respect
to release of the anti-pathogenic agent. ,
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~ Coated papers and synthetic papers may also be suitable for use
herein. For example, acceptable coated papers may be a cellulose based paper
' coated with an acrylic coating, such as Kimberly Clark's currently available
22.5 1b. per 3000 ft2 S-60857 product.
II. PapEr/Film Laminates
Paper/film laminate substrates in which the paper substrate is
generally laminated to a polymeric film are also suitable paper substrates.
They
find particular application to the uses specified above with respect to paper
substrates, but are further suitable in other applications where durability
and low
porosity are important considerations. The film component of a paper/film
laminate is usually a material such as polyethylene, polypropylene or
polyurethane, which enhances the hold-out of the substrate preventing the
coating from penetrating through the composite.
With respect to the foregoing paper and paper laminate substrates,
it should also be understood that a further consideration in selecting a
substrate
is whether the product is intended to be disposable or non-disposable, and if
disposable, the likely manner in which the product will be disposed. For
instance, consideration may be given to whether the product will be discarded
with other medically related disposable items, or discarded with other non-
medically related items in normal disposal situations, or whether there is a
possibility of disposal by flushing, as in the case of toilet seat covers.
For items which will be disposed of in medical and/or non-
medical refuse situations, biodegradability is desirable. Flushable items must
exhibit poor wet strength, and yet have good hold out. Suitable flushable
paper
substrates include those available from Coastal Paper, such as 13~i BL MG PR
HWS and 14.4~i BL MG DUNECON SH, which are light-weight bleached
coating base tissues. Non-flushable paper substrates include Coastal Papers'
10.511 BL MG HWS for which the wet strength is too high, and paper laminates
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PCT/US97/13222
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from Jen-Coat identified as Jen-Coat 191 Semi Crepe/5!/ LDPE Matte laminate ,
(low density polyethylene).
In all instances, the paper substrates described hereinabove,
including paper laminates, should be selected according to the ability of the
paper to retain the coating to a degree sufficient to ensure elimination of
bacterial or viral contamination. The product functions as a barrier to the
virus
and bacteria when dry, and actively eliminates or kills the virus or bacteria
on
contact when wet. Coated paper substrates with these qualities are suitable
for
use in a multitude of medically related and personal hygiene applications as
described hereinabove.
III. Non-Woven and Non-Woven Laminate Substrates
Non-woven substrates include such substrates as spun bonded
fabrics and two-phase fabrics. Spun bonded fabrics are those formed from
continuous filaments that have been extruded, drawn, laid on a continuous belt
in a three-dimensional arrangement, and immediately thermally bonded to form
a "web" of material. The extruded filaments have a thickness on the order of
about 20~c.
Another type of non-woven material available is a fabric called
spunlaced fabric. This fabric is a three-dimensional structure resulting from
the
hydroentanglement of staple or base fibers without any chemical or thermal
bonding, thus providing a material demonstrating excellent flexibility,
softness
and drape. The fabric may be composed of a single type of fiber, or may be a
blend of fibers, with varying content ranges. For example, the fabric may be a
rayon/polyester blend, a wood pulp/polyester blend or 100 % polyester fiber.
Fabric content is highly determinative of suitability for a specified purpose,
i.e.,
durability, strength, absorbency and other properties are directly affected by
,
fabric content.
SONTARA~, a DuPont product, is a spunlaced product available ,
in a wide range of weights and in varying fiber contents. Of particular
interest
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herein are those fabrics of a wood pulp/polyester blend, which adapt well to
use
in hospital gowns and drapes, and those of a rayon-polyester blend which
perform well as absorbent wipes and sponges, and when pre-treated, as
repellent
barrier materials having high comfort qualities.
While non-woven substrates offer many advantages, they also
represent special coating considerations. Often, non-woven substrates have
been
treated to enhance water and even alcohol repellency. Thus, many of these
fabrics are attractive as operating room fabrics. These fabrics, however, are
more likely than other substrates to experience coating absorption and
penetration. To protect against these potential problems, which may occur with
traditional web coating techniques, spray or dip coating methods have been
found herein to provide suitable alternatives. When using these methods the
subject formulation is modified, generally to achieve a thinner formula with
lower solids content.
Non-woven laminates are those materials such as the non-woven
substrates described above which have a laminate layer or a laminate backing
to
aid in solving potential absorption and penetration problems. In these
fabrics,
the non-woven material substrate is generally laminated to a film such as
polyethylene, polypropylene or polyurethane. The film enhances the hold-out
of the substrate, preventing the coating from penetrating through the non-
woven
composite.
Alternatively, the non-woven laminate may be a combination of
non-woven fabric with a microporous film laminated thereto. This microporous
film is generally a breathable film, which means that the film allows air to
penetrate, but prevents the penetration of liquids. The moisture vapor
transmission rate (MVTR) is a measure of the amount of moisture vapor that
passes through a fabric. Fabrics with high MVTR, therefore, are cooler for the
person wearing the garment than a lower MVTR fabric. Also, water vapor is
smaller than droplets of blood and is, therefore, more readily passed through
the
micropores of the non-woven substrate. The practical result of the forgoing is
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that though moisture is transported through the fabric's micropores to keep
the '
wearer of a high MVTR fabric gown comfortable, there is little danger of blood
droplets, which may carry any number of pathogens, penetrating the gown or
fabric and reaching the wearer. Specific examples of non-woven laminates
include the following substrates marketed by Polybond, Inc.: Poly-Breathe I
spunbonded polypropylene non-woven/polyethylene microporous film; Poly-
Breathe II spunbonded polypropylene/heavy duty microporous film; and Poly
Breathe Soft spunbonded polyethylene/microporous film having excellent
drapeability.
Usually, the micro-porous film side of the laminate is most easily
coated with the formulation which is the subject hereof because of superior
hold-
out which better lends itself to traditional web coating techniques. However,
the
non-woven fabric side of the laminate may be coated by alternate coating
techniques if it is desirable for functional purposes. Other suitable non-
woven
fabric laminations include Bertek's Medifilm 432, which is a laminate of
polyurethane film direct extrusion laminated onto SONTAR.A 8001 polyester
fabric. Further, the non-woven may be a wood pulp/polyester blend such as
SONTARA 8818 or 8801. The wood pulp/polyester blends are especially
engineered as fabrics for medical applications due to their softness and high
absorbency. The substrates also can be treated to repel liquids. The
laminations
cited above find particular applicability in medical garment and in wound care
fabrics or products.
The foregoing substrates are exemplary only. Any number of
other substrates will be known to the skilled artisan, and are intended to be
covered by the teachings herein, as long as the substrate maintains its
integrity
through the coating process, accepts the coating formulation and supports it
in a
manner whereby the anti-viral, anti-bacterial activity of the coating is not
adversely affected to a point where it is no longer suitable as an anti-
pathogenic
coating, and the coated substrate is suitable for adaptation or application to
use .
in the medical or personal hygiene fields.
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Coating Formulation
The subject coating formulation is an anti-viral, anti-bacterial,
. composition, having anti-HIV activity as well, which is intended for use in
all
aspects of medical applications, including dental applications, and in various
S personal hygiene applications. The composition contains as the active
ingredient
therein a combination of nonylphenoxypoly (ethylene oxy) ethanol, more
commonly known as Nonoxynol 9 or N-9, and a Polyvinyl-pyrrolidone-Iodine
complex, or PVP-I.
The Nonoxynol 9 component is a commercially available
composition which is known to exhibit spermicidal activity. It can be
purchased
from Rhone Poulenc in the liquid form.
The PVP-I component is known to exhibit anti-microbial
properties, including anti-HIV activity. It is available in the powder form
from
sources such as GAF and BASF. The PVP portion of the complex contributes
unique hydrophilic properties. The iodine portion of the complex is effective
as
a bactericide in its I2 or diatomic form.
The foregoing active ingredients, when combined and further
mixed with various additives, exhibit superior anti-HIV and anti-viral/anti-
bacterial activity, making the subject formulation highly suitable, and
desirable,
as a candidate for the coating of substrates which are used as a barrier
against
the propagation of viruses and various forms of bacteria which are highly
infectious. Because these products are intended for use in situations where
the
product may come in direct contact with the users' skin, it is imperative that
the
effectivity level of the coating be closely monitored.
Specifically, it has now been discovered that in a solution
containing the anti-viral components just described, intended for coating on
the
various substrates by general coating techniques as described herein,
sufficient
anti-viral activity is achieved along with optimal coating properties in a
solution
characterized by percent solids (non-volatiles) of 25.0 k to 35.0 l , and
ideal
viscosity, depending on the formulation used and the rheological
characteristics
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thereof, of from about 50 to 600 cps. These properties are exhibited by the
formulation described hereinafter.
The active ingredients may be combined in a ratio of PVP-I:N-9 '
of 100:0 to 0:100. A combination of the two anti-viral components provides
flexibility to change the ratio so that the fonnulation can be tailored to a
specific
application. When the intended purpose is use of a product against bacterial
infection (e.g. in a toilet seat cover), it may be advantageous to use a
greater
percentage of PVP-I. Obviously, the exact combination of active ingredients is
dependent on the end use of the product and the pathogens to be eliminated.
Generally, the subject composition contains Nonoxynol 9 and
PVP-I in combination with various agents used as filler, lubricants, binder,
suspending agent, surfactant and stabilizer. The Nonoxynol 9, or N-9,
component has the following formula:
C~Fi,9-~-O(CHzOCH20)~H
wherein n represents the number of ethylene oxide units. This polymer,
available commercially from Rhone Poulenc under the tradename Igepal CO-
630, contains at least 17 oligomers of varying ethylene oxide chain length.
The
molecule N-9 contains a hydrophobic moiety, the nonylphenol portion of the
molecule, and a hydrophilic chain composed primarily of ethylene oxide units.
The physical and chemical characteristics of the oligomers change as a
function
of chain length. For instance, in those oligomers where n = 1-6, the oligomer
is oil soluble, and these compounds exhibit greater dermal toxicity with
respect
to fibroblasts. Further, lower molecular weight oligomers, for instance, the n
=
9 oligomer, exhibit greater in-vitro spermicidal activity than those molecules
where n = 30 or higher.
The PVP-I complex represents polyvinylpyrrolidone, or povidone
USP, complexed with iodine which has been shown to exhibit anti-HIV activity ,
in addition to general anti-microbial activity. The PVP portion of the complex
is one of the most highly utilized polymers in medicine due to its safety for
human use and its hydrophilic nature when complexed with iodine at a 10% w/v
T'
CA 02301019 2003-02-04
level. A 10~ w/v PVP-I solution contains approximately 1~ of
available Iz, the I2 content being about 9-12~. The complex
efficiently delivers anti-microbial I2 (free iodine) at a
relatively non-toxic, non-irritating rate. The hydrophilic PVP
:i polymer, therefore, acts as a means for delivering free iodine to
solution from the complex which is important because the free
iodine functions to eliminate viral or bacterial pathogens,
including the HIV virus. Because commercially available PVP-I
material is in a complexed form in which a true chemical bond
1(1 apparently exists between the PVP and iodine constituents, it is
provided in a detoxified form found to be non-irritating to human
skin, thus eliminating these concerns with respect to the subject
invention.
The coating composition further includes a hydrophilic
15 polymeric binder which further functions as a dispersant or
suspension agent. Suitable agents include modified cellulose
. materials, such as methylcellulose, hydroxyethylcellulose,
hydroxymethylethylcellulose and hydroxypropylmethylcellulose
(HPMC). This agent is non-toxic and therefore safe for inclusion
20 in coatings which will come in contact with human skin.
Talcum, or natural hydrous magnesium silicate, in foliated
form, also known as talc, is included in the subject composition
as a filler and lubricating agent. Substitutes for talc include
titanium dioxide and calcium carbonate.
25 A surfactant is included in the coating composition to aid
in control of the rheology of the coating by reducing surface
tension. One nonionic surfactant suitable for use herein is
obtained by esterificatian of sorbitol with a fatty acid under
conditions which cause the splitting out of water from the
30 sorbital, leaving sorbitan. This surfactant is nontoxic and
soluble in water, alcohol and ethyl acetate. The surfactant
prepared is polyoxyethylene sorbitan monooleate. Tween BOTM is a
commercially available polyoxyethylene sorbitan monooleate
marketed by Spectrum. Other suitable surfactants will be known
35 to the skilled artisan.
CA 02301019 2003-02-04
Polyethylene glycol is added to the composition as an
excipient. This component functions as a lubricant,
plasticizer, binder and suspending agent. The polyethylene
glycol is soluble in ethanol and water, has low toxicity and
'i is a stable compound. One suitable polyethylene glycol
product is CarbowaxT"", available commercially from Union
Carbide. An acceptable molecular weight range for the
polyethylene glycol component is dependent upon the remaining
formulation components, however, CarbowaxT"" 1450 grade (average
molecular weight range 1300 to 1600) to CarbowaxT"" 8000 grade
(average molecular weight range of 7000 to 9000) is generally
suitable for the subject formulation. Further, it is
preferred to use Sentry grade product produced to meet
National Formulary (NF) and Food Chemical Codex (FCC)
specifications for food, drug and cosmetic applications.
The following general formula is suitable for use in
traditional web coating techniques, such as reverse roll, rod
coating, gravure coating,etc.
General Coating Formulation
Component Percent Composition
Active Ingredient Solution 30 - 80%
N-9 0 - 100%
PVP-I 0 - 100%
Pre-mix Solution 20 - 70%
Polyethylene Glycol solution 30 - 85%
Hydroxypropyl methylcellulose 2 - 20%
Polyoxytheylene sorbitan
compound 2 - 10%
Hydrous magnesium silicate 5 - 15%
Ethanol Solvent 0 - 30%
100.00
% solids = 20% to 35%
1G
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One embodiment of the invention relates to the preferred method
for producing the above coating composition. The coating formulation prepared
below (Formulation 2) has 71.5 % Active Ingredient Solution and 28.5 % Pre-mix
Solution, with a % solids of 31.4 % and a viscosity of between 90 and 130 cps:
Initially, a pre-mix solution is prepared comprising a polyethylene
glycol (Carbowax) solution, talc, hydroxypropyl methyicellulose (HPMC), and
polyoxyethylene sorbitan monooleate (Tween 80). The solution of Carbowax is
prepared by adding Carbowax to an ethanollwater mixture in the following
proportions:
Carbowax Solution (1A)
Component Percent
Carbowax 8000 20.0
(Sentry Grade)
Distilled Water 32.0
Ethanol 190P - 480
100.0
solids (theoretical) = 20 %
where the Ethanol 190P is a solvent blend ethanol product, available
commercially from Ashland Chemical, which contains 87 % ethyl alcohol, 4
methyl alcohol, 2 % methyl isobutyl ketone, and 3-7 % water. Other suitable
solvents include other ethanols, methanol, and mixtures of ethanol or methanol
and water.
To the Carbowax solution is added Tween 80 and Ethanol 190P
with stirring.
In a separate container, Dow Methocel E15LV hydroxypropyl
methylcellulose powder and talc TI005 dry powder are combined. In this
instance, Dow Methocel ElSLV and T1005 respectively may be used, though
other suitable commercial products will be known to the skilled artisan.
Alternatively, these powder components could be added individually directly to
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the pre-mix solution, slowly and with high shear mixing. Combining the '
powders prior to addition to the premix results in easier and more efficient
assimilation of the HPMC resin into the pre-mix. '
Once the powders are fully mixed, the mixture is added slowly to
the pre-mix solution, increasing the mixing speed as the mixture thickens.
Stirring is continued for at least 30 minutes, until a homogenous mixture is
obtained.
Pre-Mix Solution (1B)
Component Percent
Carbowax Solution ( i A) 54.6
HPMC 5.4
Tween 80 7.2
Talc T1005 11.5
Ethanol 190P 2I . 3
100.0
solids (theoretical) = 35
The foregoing pre-mix solution has a viscosity of from about 2000
to 2800 cps, and a theoretical percent solids of about 35 % .
This premix is then added to the active ingredient solution which
comprises PVP-I dissolved in Ethanol 190P (30 % solids) and N-9 dissolved in
Ethanol 190P (30 % solids) which have been combined to form the active
ingredient solution. The PVP-I solution has a viscosity of about 75 cps and
the
N-9 solution has a viscosity of about 4.2 cps. The combined solution, at 30%
solids, and a ratio of 93.3 % PVP-I to 6.7 % N-9 has a viscosity of about 60
to
70 cps.
T
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Active Ingredient Solution (1C)
Component Percent
PVP-I Solution (30%) 93.3
N-9 Solution (30%) 6.7
100.0
% solids (theoretical) = 30 %
The finished coating composition exhibits 31.4 % solids
(theoretical) and a viscosity in the range of 90 to 130 cps.
FORMULATION I
Preferred Coating Formulation
Component Percent
Active Ingredient Solution ( 1 C) 71.5
Pre-mix (1B) 28.5
100.0
% solids (theoretical) = 31.4 %
As will become apparent to the skilled artisan, there are many
variations to the foregoing, falling within the recited component ranges,
which
are equally well suited for use as described herein. For instance, a
formulation
having a lower % solids would be better suited to spray and dip coating
techniques. The foregoing is merely one embodiment of the composition,
included as a means of more fully disclosing the subject coating composition
and
a method of making the same. The foregoing solution is well suited for coating
by the reverse roll and rod coating methods on a paper or film, or suitable
laminated substrates. Generally, the coating composition, having an active
ingredient concentration of 25 % to 80 % of the coat weight on dry basis, is
coated at a coat weight of 6 to 12 oz. per 384 ft2. In the foregoing, the
active
ingredient concentration equates to about 140 to 760 p,g/cmz on a given
~ substrate.
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DESIGN ALTERNATIVES '
Alternative Coating Techniques for Coating Various Substrates
As has been shown hereinabove, many paper substrates coat well
by the reverse roll method using the General Coating Formulation with a
percent
S solids about 30 % to 32 % . Percent solids below about 10-15 % are generally
not
desirable with this technique due to high cost of lost solvent (volatiles) and
because viscosities tend to be too low in this solids range resulting in poor
coating quality and difficulty in achieving sufficient coat weight.
Conversely,
above the 50% solids range, problems with high viscosity and coating quality
can be experienced, and it can then be difficult to achieve lower coat
weights.
This, of course, is a general observation, assuming a reverse roll or other
traditional coating technique, and will change depending on the coating method
actually used.
Some substrates, however, do not wet out to the level preferred
herein with the General Coating Formulation. For example, some paper
substrates, such as Jen-Coat's 19 Ib. Semi-Crepe/5 1b. LDPE which is a
paper/film laminated substrate in which the semi-crepe paper is laminated to
low
density polyethylene, do not adequately wet out, or accept the coating. Some
non-woven laminates can also experience a problem. These instances represent
another embodiment of the subject invention wherein the percent solids of the
formulation can be lowered, which improves the wetting action of the coating
on
the substrate, and still permits an acceptable coating anti-pathogenic
activity
level. Non-woven laminates which can be successfully coated by the reverse
roll method by lowering the percent solids of the formulation to a range of
about
25 % solids include Poly-Breathe II, made by PolyBond Incorporated, which is a
breathable film composite in which spunbond polypropylene non-,woven fabric is
laminated to a heavy duty microporous film.
There are, however, some non-woven laminates such as a two-
phase wet formed non-woven substrate, available from the Dexter Corporation
as Grade 11160 Fabric (1992), and a drapable, non-woven water and alcohol
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repellent fabric, also available from Dexter Corporation, as Grade 3557 fabric
( 1993), sterilizable by ethylene oxide, steam or radiation, which are not
easily
reverse roll coatable using the subject formulation even at a lowered percent
solids range of about 20 % solids. These non-woven laminates are, however,
coatable by the rod coating method and enable use of the formulation at a 30%
to 32 % solids range, thus eliminating solvent waste problems. This is yet
another embodiment of the invention.
The following table summarizes the results of testing conducted
on various substrates with varying levels of percent solids in the coating
formulation and by the reverse roll and rod coating methods.
TABLE I
Pil ot Coating
Run
- Formulation
I at
% Sotids
Shown
Reverse Rod Coating
Roll
Coating
(50
FPM)
(50 FPM)
Substrate
~ %
Solids
of:
~31.4% ~28.0% ~25.0% ~20.0% ~31.4%
Coastal 13~Y OK
BL MG
PR I-iWS (i)
Jen-Coat Fair OK
-slight
Semi-Crepe White
Laminate
(ii) Spotting
Poly-Breathe OK
II
(Poly Bond)
(iii)
Dexter if 11160 NG - NG
(iv) Poor
Wetting
Dexter ~/ 3557 NG - NG- OK
(v) Poor but
Wetting im roved
(i) 13J! wood pulp processed with cellulosic fibers, light weight, flushable
(ii) 19;!i semi crepe/5;'! low density polyethylene laminate
(iii) spunbond polypropylene non-woven fabric/microporous film laminate
(iv) 2 phase wet formed, non-woven laminate
(v) drapable, non-woven water and alcohol repellent fabric
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A further alternative to solve coating pick-up problems on some
substrates is to use substrates which have been treated to enhance coating
acceptance. For example, certain non-woven laminates, including some
polyester non-wovenllow density polyethylene (LDPE) film lamination
substrates, exhibit poor adhesion of the coating to the substrate. Post-
treatment
of the laminate by corona treatment, which is a process in which the substrate
is
bombarded with a high voltage electrical discharge thereby causing an increase
in surface tension on the polyethylene film side of the laminate, increases
the
surface tension of the substrate, thus enhancing adhesion of the coating to
the
substrate.
The foregoing discussion and data clearly demonstrate the viability
of the subject coating formulation on many substrates and for many
applications
by optimization of the formulation, the substrate, the coating method, or a
combination thereof, the parameters being highly dependent on the particular
application for which the substrate is intended.
Using the subject formulation or composition, as described
hereinabove, there are a multitude of coating options available to the skilled
artisan. Various types of products encompassing some of these options are
exemplified herein as a means of more fully describing the parameters of the
subject invention.
Anti-Bacterial/Anti-Viral Coating
Formulations with Improved Water Resistance
In another embodiment of the invention, the subject coating
formulation may be modified to render the coating less prone to leaching, i.e.
the coating will have enhanced water resistance. The subject coating functions
by acting as a barrier to pathogenic substances when dry, and becomes
activated
when wet to immediately eliminate the bacterial or viral effect of the
pathogen.
If the coating is totally wafer insoluble, it will not be effective in killing
blood-
or fluid-borne pathogens upon contact of the coating with the pathogens.
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Therefore, the coating must be at least partially water soluble in order to
function. Tn some instances, however, it is desirable to reduce the degree of
. water solubility, thus improving water resistance and reducing the tendency
of
the coating to leach from the substrate upon contact with water or fluid.
One approach to increasing water resistance of the coating is to
add to the formulation a material which is insoluble in water, but which would
be soluble in an ethanol/water mixture, because this mixture is used as the
solvent for the formulation. One such material is zein, which is a prolamine
physically extracted from corn gluten. It forms films which are clear,
odorless,
tasteless and hard, and is suitable for human ingestion. Zein is insoluble in
water and in anhydrous alcohol, but is soluble in a mixture of the two.
The degree to which the water resistance of the coating is
enhanced by the addition of zein is a function of the concentration of the
zein
for a given substrate. For example, in a composition similar to that disclosed
hereinabove, wherein the active ingredient solution is 54.8 % by weight of the
formulation and the pre-mix is 45.2 % by weight of the formulation, zein may
be
added to the premix as a 17.6 % component of a solution which comprises
50.0% by weight of the pre-mix solution, the remainder of the prc-mix solution
comprising a carbowax solution as previously described.
FORMULATION II
Zein Water Resistant Coating Formulation
Component Percent
Active Ingredient Solution (40% solids) 54.8
PVP-I
(40 % in Ethanol 190P) 93. 3 %
N-9 6.7 %
(40 % Igepal CO-630 in Ethanol 190P)
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FORMULATION II
Zein Water Resistant Coating Formulation
Component Percent
Pre-mix Solution 45.2
Zein Solution (25 % solids} 50.0
Zein F4000 ( 17. 6)
Talc T1005 ( 4.4)
Tween 80 ( 3.0)
Ethanol 190P (60.0)
Distilled H20 ( 15.0)
Carbowax Solution (20% solids)* 50.0 %
Carbowax 8000 (20.0)
Ethanol 190P (48.0)
Distilled HZO (32.0)
100.0
% solids = 32.65
*Solution 1A from .General Formula Description
This formulation had a viscosity of 96.3 cps., well within the desired range.
The formulation was tested for water resistance by coating the
formulation on 17.S~f James River Flexpac paper substrate by the reverse roll
method. This coated substrate and the same substrate material coated in the
same manner with the coating formulation hereinabove (Formulation I), not
including the zein component, were subjected to water resistance testing for a
ten (10) minute period. The test parameters were as follows: The average
weight of the substrate sample was first determined, as was that of the same
substrate with the coating formulations, with and without zero, having been
applied. The coated sample was then placed in room-temperature tap water for
the specified test period, i.e., 1 minute, 5 minutes, 10 minutes, etc. After
the '
t
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~ test period had been completed, the sample was removed from the water bath
and excess water allowed to drain back into the bath. The sample was dried by
hanging until all draining stopped and then placed in an oven, at
approximately
110° F., to remove any remaining water. The weight of the sample was
again
measured. The amount of coating dissolved off the substrate in a specific time
in water was determined by the following calculation:
coating dissolved = (initial weight - final we~hty x 100
(initial weight - substrate weight)
The test results, as shown below, proved the zein formulation to have enhanced
water resistance. All coatings were in the coat weight range of 7 to 9 oz. per
384ft2.
Water Resistance Test Results*
Coating Formulation Percent Coating Dissolved
After 10 Minutes
Trial 1 - Formulation II 89.19 %
(with zein, at 32.65 % solids
and
96.3 cps viscosity)
Trial 2 - Formulation II 89.80 !o
(with zein, at 32.65 % solids and
96.3 cps viscosity)
Trial 3 - Formulation I 94.87
(without zein, at 31.4 % solids
and
90 - 130 cps viscosity)
Trial 4 - Formulation I 95.34
(without zein, at 31.4 % solids
and
90 - 130 cps viscosity)
* substrate = 17.5# James River Flexpac.
A second approach available to enhance the water resistance of
the formulation is to substitute an alcohol-soluble resin, or water insoluble
resin,
for the HPMC resin component of the premix.
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FORMI1LATION III
Alcohol-Soluble Resin Water Resistant Coatin Formulation
Component Percent
Active Ingredient Solution (30% solids)* 71.5
PVP-I (30 % in Ethanol 190P) 93.3 %
N-9 (30 % in Ethanol 190P) 6. 7 %
Resin Solution 28.5
I O 30 % Butvar B98 in Ethanol 190P**
100.0
solids = 30
*Solution 1C from General Formulation Description.
**Polyvinyl Butyryl resin, Monsanto.
Other resins similar to the Butvar B98 may also be used, such as
polyamide resins or cellulose-type resins. This represents yet another
embodiment of the invention.
This formulation was tested for water resistance in the same
manner as set forth with respect to Formulation II, i.e. it was coated on the
same substrate material in the same manner and at the same coat weight, and
tested in the same manner. These test results show even further improvement
over the zein results as compared to the formulation without the alcohol-
soluble
resin.
Water Resistance Test Results
Coating Percent Coating Dissolved
After 10 Minutes
Butvar B98 (Ill) 76.4
It is also possible to improve water resistance by choice of
substrate. For example, Formulation I, described above, was coated on two
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~ different substrates and then tested by the method given above for water
resistance. The test results were as follows:
Water Resistance Test Results
Substrate Percent Coating Dissolved
1 Minute 10 Minutes
James River 17.5/I Flexpac' 81.00 % 94.64
Kimberly Clark S-608572 33.09 % 65.62 %
'James River 17.5/ Flexpac is a wood pulp processed .with cellulosic fibers.
ZKimberly Clark S-60857 is a cellulosic substrate with an acrylic coating.
The foregoing test results regarding water resistance of the coating
prove that a number of methods have been identified by which this coating
property can be manipulated to achieve water resistance for a given
application
while yet maintaining acceptable anti-bacterial/anti-viral activity.
Addition of Dyes or Pigments
In still another embodiment of the invention, it is possible to add
or incorporate dyes and/or pigments into the subject coating formulation. The
active ingredients of the subject formulation tend to give the formulation a
yellow hue. While this is perfectly acceptable in some cases, for instance on
many paper substrates, some non-woven substrates which begin with a blue or
green color take on aesthetically unacceptable coloration once coated.
Further,
many users will desire certain products to exhibit specific colors, whether as
an
identifier of the producer or manufacturer, or merely as a matter of
aesthetics.
When using a dye to aid in coloration of the coated substrate, it is
preferred to add the dye to the pre-mix solution and leave the active
ingredient
solution undisturbed, thus maintaining the desired concentration of active
ingredients. For example, the following coating formulation includes Hilton
Davis FD&C Blue ~ 1, a commercially available dye, in the pre-mix solution.
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Where possible, in light of desired color, solubility constraints,
dispersability '
constraints, etc., it is preferable to use colorants, or dyes and pigments,
which
have been previously approved by the Federal Drug Administration (FDA) for
inclusion in foods, dings, and cosmetics. Unfortunately, there is no list of
colorants which are pre-approved by the FDA for inclusion in medical/hygiene
products of the type contemplated herein. Colorants pre-approved for use in
foods, drugs and cosmetics are good candidates for use herein, however, given
the likelihood that the toxicological criticality of foods, drugs and
cosmetics is
probably greater than that of the products anticipated herein, which are not
intended in most cases for ingestion or assimilation into the human body, but
are
anticipated rather to merely have limited contact with human skin.
FORMULATION IV
Die-Containing Coating Formulation
Component Percent
Active Ingredient Solution* 72,0
PVP-I (30% in Ethanol 190P) 93.3 %
N-9 (30 % Igepal CG 630 in Ethanol 190P) 6.7 %
Pre-mix Solution (50% solids) 28.0
Carbowax Solution 42.0
HPMC 4.2 %
Tween 80 5.5
Talc TI005 g. g %
Ethanol 190P 16.4
Hilton Davis FD&C Blue #/1 23.1 %
100.00
solids = 35. 6
*Solution 1 C from General Formulation description.
This coating formulation exhibits a bluish-green color, much like kelly green.
In an alternative embodiment, titanium dioxide (Ti02) may be
substituted for the talc component of the pre-mix solution prior to addition
of
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dyes and/or pigments. This technique is particularly useful when attempting to
achieve certain colors, such as indigo blue, aqua blue, or blue-green type
color.
The substitution of TiOZ for the talc component results in a premix solution
that
is very close to white. The desired dye is then added to the premix solution,
S taking into account the inherently yellow hue of the active ingredient
solution, to
achieve the desired color in the final formulation. For example, the following
pre-mix solution may be used in Formulation IV, Dye-Containing Coating
Formulation, in place of the recited Pre-mix Solution to achieve an indigo
blue
colored formulation:
FORMULATION V
Dve-Containing Coating Formulation
1S
Component Percent
Active Ingredient Solution* 72.0
PVP-I (30 % in Ethanol 190P) 93.3
N-9 (30 % Igepal CO 630 in Ethanol 190P) 6.7
Pre-mix Solution (SO % solids) 28.0
Carbowax 8000 Solution 42.00 %
HPMC 4.20
Tween 80 S.SO
TiOz 8.80 %
2S BASF Basonyl Blue 636 I 1.SS %
BASF Basonyl Red NBS40 11.SS %
Ethanol 190 P 16.40
*Solution 1 C from General Formulation description.
100.00
solids = 35 . 6 %
Another embodiment relates to a means of achieving a desired color in
the coating formulation is to disperse a pigment or pigments directly into the
~ pre-mix solution in place of the talc component without the use of Ti02. The
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pigment concentration can be adjusted to achieve control over the color
strength. '
FORMULATION VI
Dye-Containing Coatin~Formulation
Component Percent
Active Ingredient Solution* 72.0
PVP-I (30 % in Ethanol 190P) 93.3
N-9 (30 % Igepal CO 630 in Ethanol 190P) 6.7 %
Pre-mix Solution (44 % solids) 28.0
Carbowax 8000 Solution 54.6
HPMC 5.4
Tween 80 7.2 %
Sunfast Blue 15:1 (Sun Chemical) 8.8
Ethanol 190P 11.5 %
100.00
% solids = 33.9
*Solution 1C from General Formulation description.
This coating formulation takes on a yellow-green color.
Micro-Encapsulation
In yet another embodiment of the subject invention, the coating
includes the use of a micro-encapsulant. In some instances, it may be
desirable
to produce a coated substrate which exhibits a controlled release of the anti-
bacterial/anti-viral agents. Also, certain environmental or use conditions may
require enhanced stability of the coating. In those applications where these
concerns are prevalent, the coating may include a micro-encapsulation factor
to
aid in achieving the desired results.
Micro-encapsulation involves coating or sheathing a core material.
Encapsulation has been used extensively in the pharmaceutical industry, and
has '
1
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. been accomplished by both chemical and mechanical processes. Some chemical
processes include complex coacervation; polymer/polymer incompatibility; in-
situ polymerization, etc. Mechanical processes include spray drying and
fluidized bed techniques, among others.
In the subject application, the core material would be the active
ingredient combination or agent, and the encapsulation may be by polymer or
wax-type outer layer. For example, one may use a polymer/polymer
incompatibility technique wherein the active ingredient polymer (PVP) is water
soluble and the coating polymer is not water soluble. The resulting micro-
encapsulated coating exhibits enhanced stability in humid conditions and
controlled release of the active ingredient upon exposure of the coating to
wet
conditions.
One formulation which has proven suitable for use in
microencapsulation is Forrnulation III, which has 30 % solids and uses a
polymer
of polyvinyl butyryl, available commercially from Monsanto under the
tradename Butvar B98. As might be expected, due to the water resistant
characteristic of the polymer microencapsulant, this formulation enhances the
water resistance of the formulation as reported hereinabove.
FORMULATION III
Butvar B98 Microenca~sulation CoatinE Formulation
Component Percent
Active ingredient Solution (30 % solids)'" 71.5
PVP-I (30 % in Ethanol 190P) 93.3
N-9 (30 % in Ethanol 190P) 6.7
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Resin Solution 28.5
30% Butvar B98 in Ethanol 190P**
100.0
% solids = 30 %
*Solution 1 C from General Formulation description.
**Polyvinyl Butyryl resin, Monsanto.
While this formulation includes a polyvinyl butyryl resin, other
suitable microencapsulation resins are commercially available. Other resins
may
include polyamide and cellulose-type resins, among others, which exhibit a
time
controlled dissolution, thus ensuring continued release of the agent over
extended periods of time for extended user protection.
Incorporation of the Formulation into Non-Woven Laminates
In still another embodiment of the current invention, the
formulation or derivatives of the formulation can be incorporated directly
into
the laminate during the lamination process as opposed to the use of the
formulation as only a surface coating composition. Several techniques may be
used to achieve this end result, including spraying the formulation into the
fibers
during the lamination process, blowing the formulation into the fibers during
the
lamination process, and spraying or applying the formulation onto the fibers
during the process.
For example, the formulation may be used in conjunction with
melt blown technology/processing to produce a web having the formulation
embedded therein. Specifically, in one embodiment of this aspect of the
invention the formulation, diluted to an appropriate percent solids of 25 %,
was
air blown into the fibrous stream, thus being incorporated into the web as it
is
being formed in a more or Iess three-dimensional manner.
Also, the formulation may be coated on a monolithic film, which
is a thin breathable film laminated to a non-woven fabric or substrate, as
CA 02301019 2000-02-10
WO 99105909 PCT/US97/13222
-33-
. discussed hereinabove. Alternatively, the film substrate portion of the
laminate
can first be- coated with the anti-bacterial/anti-viral formulation. After
coating,
the film can be laminated to the non-woven substrate, thus creating a more-or-
less sandwich-type arrangement.
Spray and Dip Coatings with Anti-BacteriallAnti-Viral Properties
In yet another embodiment of the subject invention, the coating
formulation is spray or dip coated on specific preformed articles, as opposed
to
sheeting or fabric. These coating methods, while they are suitable for the
substrates thus far discussed in a limited sense depending on porosity, are
readily applicable to the coating of articles or objects. By articles is meant
items intended for use in medical applications, such as catheters and surgical
gloves.
When using these coating methods, and depending upon the article
to be coated, the active ingredient solution described above may be used
directly
on the article without the addition of the premix solution. Alternatively, the
active ingredient solution may be diluted with ethanol to a percent solids of
about 12 % to 20 % , which aids in capability to use the spray coating method,
as
well as dip coating. Of course, the full formulation as recited previously
herein
may be used if desired and exhibits good results at 10-20 % dilution. These
coating techniques may be necessary with certain non-woven substrates, as
stated
above, due to problems with absorbency and coating penetration.
The following shows the results of using a spray coating with and
without the premix solution in ternls of I2 concentration levels found to be
effective for the purpose set forth herein. In both instances, the formulation
tested was coated onto a non-woven fabric, Precision S019/08833. Sample A
below was coated with Fornlulation I diluted to 10 % solids, and Sample B was
coated with only the Active Ingredient component of Formulation I diluted to
10 % solids without any premix.
CA 02301019 2003-03-05
34
S m Coat WeiGht a~ Conc~~ntrat~fon
Sample A 7-8 oz, per 384 ft' 41.34 ~Cg/cm~
Sample s 5-6 oz, per 384 ft; 45,88 ~.g/cmz
Sample 8 required the use of a lower coat weight in order to
S achieve an equivalent I2 concentration given that no premix ways
used and the Active Ingredient concentration is therefore
higher.
'Ose of Pozmulation as Disyn~sctaat Spray
One more embodiment of the subject invention involves tae
use of the subject active ingredient so~.ution formulation in a
diluted condition as a disinfecting spray, directly on
surfaces which may be easily contaminatc:d_ Such surfaces
include table and counter tops where fluid and tissue sampler
are stored or analyzed, and containers i:or sample storage,
such as holding trays, cool storage cons:ainers, carrying
cases, etc_ Further, there is a need for such a spray for
personal hygienic use, such as in public restroom facilities.
Dilution of the Solutiozz to a 5o to 10% solids ranges ensure;a
ease of use while yet maintaining the required level. of anti-
viral/anti-bacterial activity. Such a spray would not be
toxic to human tissue which may come in contact with the spray
during or immediately after use.
waluatian o~ eoati.ng Formulation
The following samples, coating ancL substrates as
specified in TABLE II, at the stated percent solids, Iz
concentratior~ and coat weight were evaluated for HiV-
inactivating properties. Using the test protocol set Forth is
~Evaluation of Antiviral Drugs and Neutralising Antibodies to
Human Immunodefieiency virus 8y a Rapid and Sensitive
Mzerofilter Infection Assay", J. C ~,n. Mi~ob?oloav. 1988,
Vol. 26: 231-235, virus suspensions were placed on various
samples and remained on the samples fox 1-2 minutes, after
which a small amount of suspension was
CA 02301019 2000-02-10
WO 99/05909 . ~ PCTNS97/13222
-35-
cultured for detection of infectious virus. The cultures were maintained for
twelve (12) days, which is sufficient to detect as little as one (1)
infectious vims
. particle.
The cells were observed periodically over the twelve day
incubation period, and as seen under light microscopy, the results were
recorded
as "+" (any number of syncytia present) or "-" (no syncytia present). Cultures
that remain free of syncytia after twelve days indicate that the inoculum
contained no infectious virus. Further test to confirm the absence of
infection
involved use of the immunoassay used to detect the HIV p24 antigen.
The results of these tests showed the HIV was completely
inactivated upon contact with each coated sample (Examples 1-8), but was not
inactivated by contact with control samples (Examples 9-12). In these tests,
virus that came in contact with control samples was detected very early by the
presence of syncytia after five (5) days. In contrast, a virus inoculum that
came
in contact with coated samples remained free of syncytia for twelve days and
had no detectable HIV p24 antigen.
CA 02301019 2000-02-10
WO 99/05909 ~ ~ PCT/US97/13222
- 36 -
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CA 02301019 2000-02-10
WO 99/05909 . PCT/US97/13222
- 37 -
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CA 02301019 2000-02-10
WO 99/05909 ~ ~ PCT/US97/13222
-38-
A further study was conducted to determine the self sanitizing .
activity of an antimicrobial coated paper according to the subject invention.
The
test system used has been used historically for this type of study and will
allow '
the data to be compared to that of other compounds. The study was conducted
according to the protocol entitled, "Evaluation of Self Sanitizing Activity of
an
Antimicrobial Coated Paper." The test organism was Staphylococcus aureus
ATCC 6538.
Two jars were prepared, each containing ten 15/s" x 15/s" square
swatches of the control article, Example 21, and two jars were prepared, each
containing ten 15/s" x 15/a" square swatches of the test article , Example 22.
One
jar of each set was labeled "30 seconds" and the other "120 seconds".
Cultures S. aureus ATCC 6538 were added to the swatches in
each bottle. The Samples were neutralized after desired exposure, 30 seconds
or
120 seconds in 100 ml of phosphate buffer neutralizer fluid.
The samples were plated and all plates were incubated at 37 t 1 °
C for 48 hours prior to counting. The results are presented in Table III
below.
The material identified as Example 22, Formulation I, on tissue
paper (toilet seat cover tissue), an orange translucent paper, achieved a 99.9
reduction in a 30 second exposure and a > 99.999 % reduction after a 120
second exposure compared to the number of S. aureus recovered from the
untreated control swatches, Example 21, immediate (30 second) contact time.
The percent reduction of bacteria by antimicrobial treated substrate was
calculated as follows:
Percent Reduction = B - A x 100
100
A = The number of bacteria recovered from the treated substrate, Example 22
in the jar incubated over the desired contact period.
B - The number of bacteria recovered from the untreated control substrate
Example 21, in the jar immediately after inoculation (30 seconds).
'
T
CA 02301019 2000-02-10
WO 99/05909 ~ ~ PCT/US97/13222
-39
TABLE III
Self Sanitizing Activity of Antimicrobial Coated Paper
L
ExampleExposure 10 10''10'=10''10'310'AverageNo.org/
time
(seconds) CFUImI tissue
neutralizersample*
21 30 27 0 1 3.3 3.3
x 105 x
10'
39 10 0
21 120 32 4 1 3.4 3.4
x 103 x
10'
35 4 0
22 30 27028 2 3.2 3.2
x 10~ x
10'
27636 4
22 120 2 0 0 1.0 1.0
x 10 x
10'
0 0 0
*Number of organismltissue sample - Number per ml neutralizer x lUU ml
neutralizer
Test Organism Inoculum Counts ChU/ml
10-6 10-' 10~a 3.0 x 109
Staohvlococcus aureus ATCC 6538 TNC* TNC 33
TNC TNC 27
*Too numerous to count.
The subject invention has been described with reference to
specific substrates, coating formulations, testing and test results, and
processing
techniques, all of which are included to better enable the skilled artisan to
duplicate the subject invention in all its many forms. It is not intended that
the
invention be limited by these examples, but rather that it be accorded the
full
breadth of the teachings herein, including all variations and permutations
thereof
CA 02301019 2000-02-10
WO 99/05909
PCT/US97/13222
-40-
which are obvious to the skilled artisan given the content of this disclosure
and
which fall within the scope of the appended claims.
