Note: Descriptions are shown in the official language in which they were submitted.
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POLYMER-BASED ANTIMICROBIAL AGENTS, METHODS OF MAKING SAID
AGENTS, AND PRODUCTS AND APPLICATIONS USING SAID AGENTS
BACKGROUND OF THE INVENTION
FIELD OF THE INVENTION
[0001] The invention relates to antimicrobial agents, products incorporating
such
agents, and methods of making such products. More particularly, the invention
relates
to polymer-based antimicrobial agents.
STATE OF THE ART
[0002] Silver and silver salts are commonly used as antimicrobial agents. An
early
medicinal use of silver was the application of aqueous silver nitrate
solutions to prevent
eye infection in newborn babies. Silver salts, colloids, and complexes have
also been
used to prevent and to control infection. Other metals, such as gold, zinc,
copper, and
cerium, have also been found to possess antimicrobial properties, both alone
and in
combination with silver. These and other metals have been shown to provide
antimicrobial behavior even in minute quantities, a property referred to as
"oligodynamic."
[0003] Metallic antimicrobials function by releasing metal ions into the
microbe. The
released ions react with protein and other anions (negative charged species)
in the
microbe and render the protein insoluble and thereby inactive. The inactive
protein
perturbs cellular function, disrupts membranes and prevents the normal
activity and
reproduction of DNA thereby essentially killing the microorganism.
[0004] U.S. Pat. No. 6,306,419 to Vachon et al. discloses a polymer-based
coating
comprising a styrene sulfonate polymer with a carrier molecule bound to silver
ion
incorporated therein. The styrene sulfonate polymer is prepared by reacting an
acetyl
sulfate sulfonation agent with a styrene copolymer in 1,2-dichloroethane
(DCE). The
coating is hydrophilic such that it retains a relatively large amount of water
or water-
containing fluid. There are several disadvantages to this composition. One
such
disadvantage is that larger quantities of the silver metal are required to
provide
effective antimicrobial activity. A second disadvantage is that the carrier
molecule is
required which renders it more expensive as well as more difficult to dispose
of the
carrier byproduct. A third disadvantage is that a solvent other than water
(e.g. DCE) is
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required to prepare the polymer matrix. Such solvents are typically hazardous
because of their reactive nature and thus require special care in handling and
disposing of such solvents, which limits the widespread acceptance of such
antimicrobial polymers in many applications.
SUMMARY OF THE INVENTION
[0005] It is therefore an object of the invention to provide a polymer-based
antimicrobial agent that is readily soluble in a water solution.
[0006] It is also an object of the invention to provide such a polymer-based
antimicrobial agent that does not require relatively large quantities of the
metal in order
to provide effective antimicrobial activity.
[0007] It is another object of the invention to provide methods of
incorporating such
an antimicrobial agent as part of a product or service, such as a paper
product, for
mold abatement in residential and/or commercial applications, or for treating
and/or
preventing citrus canker.
[0008] In accord with these objects, which will be discussed in detail below,
the
antimicrobial agent of the present invention includes a water-soluble polymer
and
oligodynamic metal ions which interact with counter-ions of the polymer such
that the
metal ions are bound to corresponding counter-ions. The water-soluble polymer
controls a sustained release of the metal ions. The oligodynamic metal ions
preferably
include small size metal particles (e.g., nano-sized silver particles) that
ionically bond
or are electrostatically bound to the water-soluble polymer as well as metal
ions
derived from one or more water-soluble oligodynamic metal compositions (e.g.,
metal
sulfates and/or metal nitrates). The small-size particles can aid in reducing
the
photosensitivity of the agent, and thus counter the proclivity of the agent to
change
color when subjected to light. The agent may also include one or more acids,
including
organic acids (such as sulfates, carboxylic acids, amines, hydroxyls,
nitrates, and
phosphates) and/or non-organic acids (such as boric acid and dioctylborate).
This
allows the total concentration of oligodynamic metal in the agent to be
reduced
significantly while maintaining or even enhancing antimicrobial activity.
[0009] Additional objects and advantages of the invention will become apparent
to
those skilled in the art upon reference to the detailed description.
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DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0010] The following definitions are used in the description below. The terms
"colloid" and "colloidal" refer to a solution consisting of particles
suspended in a liquid
medium. An "ion" is an atom or a group of atoms that has acquired a net
electric
charge. The term "ionic" refers to a condition where an ion has an electric
charge. An
"electrostatic charge" is a charge that can be induced in a substance, for
example,
metallic silver particles, by passing a current over the substance. An
"electrostatic
attraction" is when a substance or particle with an electrostatic charge is
attracted to a
second substance which contains the opposite charge to the substance. "Water-
soluble" means that the composition has a solubility of at least 2g in 100g of
water at
room temperature. "Small size" in reference to metal particles means metal
particles
that have a size less than 1 pm in diameter and more preferably less than 0.01
pm in
diameter. "Nano-size" or "Nano" in reference to metal particles means metal
particles
that have a size between 1 nm and 100nm in diameter.
[0011] According to the invention, an antimicrobial agent is realized from a
water-
soluble polymeric substance that has pendant hydrophilic groups that are
capable of
binding with one or more oligodynamic metal ions. Preferably, the hydrophilic
groups
of the polymer are capable of binding with one or more positively charged
oligodynamic metal ions. Therefore, it is preferred that the water-soluble
polymeric
substance has negatively charged hydrophilic groups such as sulfates,
phosphates,
nitrates, carboxylates and the like. The water-soluble polymeric substance is
dissolved
in an aqueous solution. The aqueous solution preferably comprises water
without any
alcohols or other organic solvents. However, the aqueous solution can include
one or
more alcohols or other organic solvents (e.g., m-pyrol, dimethylformamide,
dimethylacetamide, dimethyl sulfonamide, tetrahydrofuran, mixtures of the
above,
mixtures of the above with swelling solvents such as diethyl ether, xylene,
toluene and
the like) preferably in a range between 5% and 50% by weight. One or more
compositions that include an oligodynamic metal are added to the polymeric
aqueous
solution. The oligodynamic metal(s) can be a noble metal (such as Ag, Au, Pt,
Pd, Ir)
or a heavy metal (such as Cu Sn, Sb, Bi and Zn). Preferably, the one or more
oligodynamic metal compositions include small size metal particles (most
preferably,
nano-sized silver particles) that carry an electrostatic charge and that
dissolve or
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disperse in the polymeric aqueous solution and ionically bond to the
hydrophilic group
of the polymer. Such small size metal particles can also remain suspended as a
colloid in the polymeric aqueous solution wherein the electrostatic charge
carried by
the small size metal particles can maintain the particles within the polymer
matrix (in
contrast to residing solely in solution) by electrostatic attraction. The one
or more
oligodynamic metal compositions added to the polymeric aqueous solution also
preferably include at least one water-soluble metal composition of an
oligodynamic
metal that dissolves in the polymeric aqueous solution and ionically bonds to
the
hydrophilic group of the polymer. One or more acids (e.g., organic acids and
inorganic
acids) can be added to the mixture.
[0012] The range of total solids dissolved in water can be from 0.1 % to 5%,
preferably from 0.3% to 3% and more preferentially from 0.5 to 2.5%. Looking
now
only at the solid components without water, the range of small-size metal
particles
(e.g., nano-sized silver particles) is preferably from 0.05 to 5% and most
preferably
from 0.5 to 3%; the range of water soluble polymer is preferably from 1 to
20%, and
most preferably from 5 to 6%; and the range of other oligodynamic metal
compositions
preferably in a range from 10 to 25%. The remaining solid content includes
acids,
organic and inorganic, that can comprise 50% to 75%, and most preferably from
70 to
75% of the solids component. This combination of reagents allows the total
concentration of oligodynamic metal in the polymeric aqueous solution to be
reduced
significantly while maintaining or even enhancing antimicrobial activity.
[0013] Examples of hydrophilic polymers which may be used to form the
compositions include, but are not limited to, polyurethanes, including
sulfonated
polyether polyurethanes, sulfonated polyester polyurethanes, sulfonated
polyurethaneureas, and their copolymers, especially the polyethleneoxide
copolymers;
polyvinylpyrrolidones; polyvinyl alcohols; polyethylene glycols and their
copolymers;
polypropylene glycols and their copolymers; polyoxyethylenes and their
copolymers;
polyacrylic acid; polyacrylamide; carboxymethyl cellulose; cellulose and its
derivatives;
dextrans and other polysaccharides; starches; guar; xantham and other gums and
thickeners; collagen; gelatins; and other biological polymers. All the of
these
hydrophilic polymers can be reacted or co-polymerized with charged moieties to
render
them both water soluble as well as ionically charged. Examples of these
charged
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moieties include, sulfonation of the aromatic rings on aromatic polyurethanes;
addition
of methacrylic acid in the vinyl-based polymers. Also included are normally
hydrophobic polymers that are rendered both hydrophilic and anionic by the
addition of
functional groups; for example, polystyrene is hydrophobic but can be rendered
water
soluble by sulfonating the styrene group. Similarly, polyethylene terepthalate
(PET)
can be rendered hydrophilic and anionic by sulfonating the terepthalic groups.
The
preferred polymer is water soluble polystyrene with its copolymers, such as
sulfonated
polystyrene co-maleic acid.
[0014] The antimicrobial agent of the invention is illustrated in the
following
example. A water-soluble sulfonated polystyrene is dissolved in water. Nano-
size
silver particles are added to the sulfonated polystyrene water solution and
mixed
together. The silver particles carry a positive electrostatic charge and
dissolve or
disperse in the polymeric aqueous solution and interact with the sulfonated
polystyrene
by ionic bonding wherein the sulfonate groups of the sulfonated polystyrene
are the
counter-ions to positively-charged silver ions. In this manner, the polymer
controls a
sustained release of the positively-charged silver ions. The silver particles
can also
remain suspended as a colloid in the polymeric aqueous solution wherein the
positive
electrostatic charge carried by the silver particles can maintain the silver
particles
within the sulfonated polystyrene matrix (in contrast to residing solely in
solution) by
electrostatic attraction. In this case, the positively electrostatically
charged nano-sized
silver particles are attracted to the polar sulfonate groups of the sulfonated
polystyrene. Advantageously, the nano-size silver particles aid in reducing
the
photosensitivity of the resulting composition, and thus counter the proclivity
of the
antimicrobial agent to change color when subjected to light. It is therefore
desirous that
when nano-sized silver particles are used, the silver ion-bound silver is
reduced
accordingly. In other words, if more nano-sized silver particles with
electrostatic charge
is used, then other silver moieties such as colloidal silver salts or silver
ion, from, for
example, silver nitrate or silver sulfate can be reduced in quantity.
[0015] Other water-soluble metal compositions that include an oligodynamic
metal
(or solutions based thereon) are added to the silver/sulfonated polystyrene
water
mixture and mixed together. Preferably, such water-soluble metal compositions
include metal sulfates (such as copper (11) sulfate or zinc sulfate) and/or
metal nitrates
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(such as silver nitrate, copper (II) nitrate and/or zinc nitrate). The ions of
the
oligodynamic metal composition(s) react with counter-ions of the polymer such
that the
metal ions are ionically bound to corresponding counter-ions, and the polymer
controls
a sustained release of the metal ions.
[0016] One or more organic acids can be added to the oligodynamic
metal/sulfonated polystyrene/water mixture and mixed together. This allows the
total
concentration of oligodynamic metal in the mixture to be reduced significantly
while
maintaining or even enhancing antimicrobial activity. Examples of organic
acids
include citric acid, malic acid, ascorbic acid, salicyclic acid, acetic acid,
formic acid and
the like. In addition to the organic acids, other mildly acidic acids can also
be used in
this cocktail such as boric acid, dioctylborate, and the like.
[0017] Table 1 shows various concentrations of colloidal silver, metal
compositions
and acids that are mixed and reacted to a water-soluble sulfonated polymer
carrier
(showing actual amounts used and percentages).
Chemical Grams Percent (Wt/Wt) Percent (Wt/Wt)
including water without water
nano-sized silver 0.050 0.005 2.444
sulfonated polystyrene 0.120 0.012 5.865
copper (II) sulfate 0.203 0.020 9.922
zinc sulfate 0.203 0.020 9.922
boric acid 0.490 0.049 23.949
malic acid 0.490 0.049 23.949
citric acid 0.490 0.049 23.949
water 1000 99.796
Total 1002.046 100 100
[0018] The specific example of Table 1 employs divalent metals; however,
monovalent or multivalent metals can also be used. Also note that when the
organic
carboxylic acids shown are mixed with the sulfonated polymer and the
oligodynamic
metal composition, a competing reaction occurs where some portion of the metal
will
couple with the sulfonated polymer and another portion of the metal will
couple with the
organic carboxylic acid(s). In the case where the metal couples with the
sulfonated
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polymer, the counter ion is the sulfonate group on the polymer. In the case
where the
metal couples with the organic carboxylic acid(s), the counter ion is the
organic
carboxylic acid. The result of this competing reaction will depend on the
stoicheometry, relative affinity and strength of the ionic bond.
[0019] The liquid mixture of materials described above can be dried and ground
to a
fine powder and commercialized as a powdered-form antimicrobial agent. In this
case,
the solid content of the powdered-form antimicrobial agent preferably includes
the
following:
- small-size metal particles (e.g., nano-sized silver particles) in a range
preferably from 0.05 to 5% and most preferably from 1 to 3%;
- water soluble polymer in a range preferably from 1 to 20%, and most
preferably from 5 to 7%;
- acids in a range preferably from 10 to 75%, and most preferably from 70
to 75%; and
- other oligodynamic metals in a range preferably from 5 to 25%.
[0020] With such product, the user need only dilute the powder in an aqueous
solution (which preferably includes only water but can include other solvents)
to the
desired concentration and spray, dip or drop the solution onto the substance
to be
coated. The powder may also be diluted in a water solution (or solvent
solution) and
added as part of an admixture during formation of the end product. For
example, the
admixture may be a pulp that is processed to form a paper product. Here the
solids
content can range from 0.001 to 10%; preferably 0.1 to 2% of the solution used
to coat
the product. When the water evaporates, a thin film of polymer remains on the
substrate where the thin polymer film binds the anti-microbial agents. In such
applications, the ions of the oligodynamic metal compositions therein interact
with
counter-ions of the water-soluble polymer such that the metal ions are bound
to
corresponding counter-ions and the polymer controls a sustained release of the
metal
ions.
[0021] The powdered-form antimicrobial agent of the present invention has many
potential applications, including the abatement of mold in residential and
commercial
applications as well as for treatment and prevention of citrus canker in
citrus groves.
When used for mold abatement, the powdered-form antimicrobial agent as
described
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above is dissolved in an aqueous solution, which is applied in spray form onto
wallboard, walls, floors, ceilings, or other home/building structural members.
When
used for treatment and prevention of citrus canker, the powdered-form
antimicrobial
agent as described above is dissolved in an aqueous solution, which is applied
in
spray form onto the leaves and/or branches and/or trunk of the citrus tree.
For citrus
canker applications, the solids concentrations of the powdered-form
antimicrobial
agent in the spraying mixture can range from 0.001 to 10%, and preferably from
0.1 to
2%. It is preferable that the mixture also contain a tackifier to help stick
the
antimicrobial mixture to the leaves and/or branches and/or trunk of the tree.
An
exemplary tackifier for this application includes one or more water soluble
substances
that are sticky; such as syrup (maple, corn, etc.), tree sap, polysaccharides,
honey,
vegetable oil derivatives and the like. The concentration of tackifier may
comprise 0.1
to 2% of the diluted formulation. In addition, the viscosity of the solution
may be
increased, which will help suspend the additives in aqueous solution to help
in
spraying applications of the system. Thickening can be accomplished by adding
more
water soluble polymer or thickeners such as gums (agar, xanthum, guar, gellan,
pectin), polysaccharide, gelatin, corn starch, and the like. The amount of
thickener can
range from 0.2 to 2%, with 0.5% of the total bath weight.
[0022] There have been described and illustrated herein antimicrobial agents,
products incorporating said agents and methods of making the antimicrobial
agents
and products incorporating them. While particular embodiments of the invention
have
been described, it is not intended that the invention be limited thereto, as
it is intended
that the invention be as broad in scope as the art will allow and that the
specification
be read likewise. It will therefore be appreciated by those skilled in the art
that yet
other modifications could be made to the provided invention without deviating
from its
spirit and scope as so claimed.
