Note: Descriptions are shown in the official language in which they were submitted.
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IMPROVED LIQUID COMPOSITION FOR CLEANING, SANITIZING AND/OR
DISINFECTING
FIELD
Aspects of the present invention relate to multifunctional cleaning and/or
antifouling
compositions comprising H202 and a composite hydrogel formulation of pluronic
acid,
wherein the composition is in liquid form at room temperature. The
compositions described
herein inhibit microbes and inflammation in a subject and are particularly
useful for dermal
sanitizing, oral-laryngeal sanitizing, nasal sanitizing, in oral prophylaxis
and periimplantitis
treatment, implant health maintenance, in periodontitis and periodontal
health, in wound care
or chronic ulcer care.
BACKGROUND
Biological surfaces like skin and mucosa and/or biomaterial surfaces are in
constant contact
with and frequently colonized by a plethora of microorganisms and virus. They
therefore
frequently require cleaning and/or sanitizing with compositions that are
antibacterial and/or
antiviral without causing harm to the biological tissue in question and
preferably without
causing microbial and/or viral resistance.
In particular, the skin of the body, such as but not limited to on the hands,
the feet, or the
face is often exposed to microorganisms and needs to be cleaned, sterilized
and/or sanitized
regularly to inhibit settlement and/or transfer of pathogens and/or microbes
and/or viruses.
Hand sanitizers
A hand sanitizer is a liquid or gel, typically used to decrease infectious
agents on the hands.
Formulations of the alcohol-based type are preferable to hand washing with
soap and water
in most situations in the healthcare setting. It is generally more effective
at killing
microorganisms and often better tolerated than soap and water. They are
typically available
as liquids, gels, wipes and/or foams.
Alcohol-based versions typically contain some combination of isopropyl
alcohol, ethanol
(ethyl alcohol), or n-propanol. Versions that contain 60 to 95% alcohol are
considered most
effective. Hand sanitizers containing at least 60% alcohol or containing a
"persistent
antiseptic" kill many different kinds of bacteria, including antibiotic
resistant bacteria and TB
bacteria, but are less effective against virus.
In general, alcohol-based hand sanitizers inhibit a variety of microorganisms
but not spores.
Some versions contain compounds such as glycerol to prevent drying of the
skin. Non-
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alcohol-based versions may contain benzalkonium chloride, chlorhexidine
gluconate or
triclosan. Care should be taken as they are flammable.
Alcohol-based hand sanitizers have been commonly used in Europe since at least
the
1980s. The alcohol-based version is on the World Health Organization's List of
Essential
Medicines, the safest and most effective medicines needed in a health system.
The
wholesale cost in the developing world is about US$1.40-3.70 per bottle.
One well documented draw-back with commercially available hand-sanitizers is
that the
alcohol in hand sanitizers may not have the 10-15 seconds exposure time
required to
denature proteins and lyse cells. Further, it is often applied in too low
quantities (0.3 ml) or in
too low concentrations. In environments with high lipids or protein waste
(such as food
processing), the use of alcohol hand rubs alone may not be sufficient to
ensure proper hand
hygiene.
To solve this, there are new alcohol gel sanitizers marketed as alcohol rub
sanitizers, which
kill most bacteria, and fungi, and stop some viruses. Alcohol rub sanitizers
containing at
least 70% alcohol (mainly ethyl alcohol) kill 99.9% of the bacteria on hands
30 seconds after
application and 99.99% to 99.999% in one minute. Still, they are notably less
effective
against virus.
90% alcohol rubs are more effective against viruses than most other forms of
hand washing.
Isopropyl alcohol will also kill 99.99 % or more of all non-spore forming
bacteria in less than
seconds, both in the laboratory and on human skin. 90% alcohol rubs are highly
25 flammable and have a potential for abuse, but are necessary to use to kill
especially viruses,
including enveloped viruses such as the flu virus, the common cold virus,
coronaviruses, and
HIV, though is notably ineffective against the rabies virus.
Hydrogen peroxide
30 Hydrogen peroxide (H202) is a very pale blue liquid which appears
colourless in a dilute
solution, slightly more viscous than water. It is a weak acid. It has strong
oxidizing properties
and is therefore a powerful bleaching agent that is mostly used for bleaching
paper but has
also found use as a disinfectant and as an oxidizer. Hydrogen peroxide in the
form of
carbamide peroxide is widely used for tooth whitening (bleaching), both in
professionally-
and in self-administered products.
Hydrogen peroxide is unstable and slowly decomposes in the presence of light.
Because of
its instability, hydrogen peroxide is typically stored with a stabilizer,
typically
organophosphates, sodium pyrophosphate, sodium phytate or sodium citrate, in a
weakly
acidic solution in a dark coloured bottle.
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Hydrogen peroxide may be used for the sterilization of various surfaces,
including surgical
tools and may be deployed as a vapour (VHP) for room sterilization. H202
demonstrates
broad-spectrum efficacy against virus and microbes including, but not limited
to, bacteria,
yeasts, and bacterial spores. In general, greater activity is seen against
Gram-positive than
Gram-negative bacteria though; however, the presence of catalase or other
peroxidases in
these organisms may increase tolerance in the presence of lower
concentrations. Higher
concentrations of H202 (10 to 30%v/v) and longer contact times are sometimes
required for
sporicidal activity.
Hydrogen peroxide is seen as an environmentally safe alternative to chlorine-
based
bleaches, as it degrades to form oxygen and water and is generally recognized
as safe as
an antimicrobial agent by the U.S. Food and Drug Administration (FDA).
Historically, hydrogen peroxide was used for disinfecting wounds. Today, it is
thought to
inhibit healing and to induce scarring, because it destroys newly formed skin
cells at high
concentrations. This is understood to be caused by the drying-out effect of
peroxide.
One study found that only very low concentrations (0.03%v/v solution, this is
a dilution of
typical 3%v/v Peroxide by 100 times) may induce healing, and only if not
applied repeatedly.
A 0.5%v/v solution was found to impede healing. Recently, new studies have
however
shown that peroxide is an important and intrinsic part of the cellular
signalling and defence
system, generating a signal that activates local defence cells in response to
infections and
insults. In line with this it is also now known that cells employ peroxide
directly to kill
microbes and virus in their immediate vicinity. Because of this knowledge,
peroxide has
gained renewed attention as a biologically active sanitizing substance.
Pluronic acid
Pluronics0 or poloxamers are tri-block copolymers of poly(ethylene oxide)-
poly(propylene
oxide)-poly(ethylene oxide) (PEO-PPO-PEO). This group of synthetic polymers is
thermo-
reversible in aqueous solutions. The sol-gel transition is governed by the
composition,
molecular weight and concentration of each constituent block polymer. The
hydrophilic
ethylene oxide and the hydrophobic propylene oxide give pluronics an
amphiphilic structure
¨ meaning it has a polar, water-soluble group attached to a nonpolar water-
insoluble
hydrocarbon chain. Amphiphilic block copolymer molecules self-assemble into
micelles (a
packed chain of molecules) in aqueous solution. Micelle formation is
temperature dependent
and affects the degradation properties of the biomaterial: below a certain
characteristic
temperature, known as the critical micelle temperature, both the ethylene and
propylene
oxide blocks are hydrated, and the PPO block becomes soluble.
Pluronics can be found either as liquids, pastes or solids. Due to their
amphiphilic
characteristics (presence of hydrophobic and hydrophilic components),
pluronics possess
surfactant properties which allow them to interact with hydrophobic surfaces
and biological
membranes. Being amphiphilic also results in the ability of the individual
block copolymers,
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known as unimers, to combine and form micelles in aqueous solutions. When the
concentration of the block copolymers is below that of the critical micelle
concentration
(CMC), the unimers remain as molecular solutions in water. However, as the
block
copolymer concentration is increased above the CMC, the unimers will self-
assemble and
form micelles, which can take on spherical, rod-shaped or lamellar geometries.
Their shapes
depend on the length and concentration of the block copolymers (i.e. EO and
PO), and the
temperature. Micelles usually have a hydrophobic core, in this case the PO
chains, and a
hydrophilic shell, the EO chains.
-: =
OH CH 2
<
Pluronic ' 1-127
Pluronic F-127, also known as Poloxamer 407, is often used in tissue
engineering because
of the commercial availability of a consistent product that will undergo a sol-
gel transition
near physiological temperature and pH. A disadvantage of Pluronic F-127 is its
fast
degradation rate in vivo. To overcome this problem, Pluronic F-127 is
frequently crosslinked
with another a-hydroxy or amino acid in order to alter the chemical structure
of its
depsipeptide unit.
Pluronic acids form thermo-sensitive hydrogels, which are typically stabilized
by addition of
high-molecular-weight acids, such as hyaluronic acid.
Studies have documented the positive effects of pluronic acid formulations in
reducing
inflammation, protect tissues against damage and hinder microbial adhesion.
Furthermore, it
is EMA and FDA approved, completely biocompatible and safe to use clinically
with no
known harmful effects in human cells.
Still, it is hard to apply as a cleaning agent because it will automatically
form a stable gel at
over 18 C, or even between temperatures of 12-20 C (see figure 1) dependent of
its
concentration, which makes it unsuitable to use in small passages and/or for
use on rough
surfaces or at body temperature and does not lend it to application with a
syringe.
Accordingly, the need for additional cleaning and/or sterilizing and/or
debriding
compositions, which can be used to disinfect, sterilize or clean, prevent
fouling and/or
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refouling of a fouled biological surface and/or a biomaterial surface, such as
the mucosa of
the oral or nasal cavity of a subject, or the exposed outer skin of a subject,
such as hands
and feet, is manifest.
5 SUMMARY
Aspects of the present invention relate to an antimicrobial and/or anti-viral
composition for
cleaning and/or sterilizing a biological surface and/or a biomaterial surface
e.g. in
situ, comprising at least two components:
(a) H202 at a final concentration of between 0.1 ¨ 7%v/v, and
(b) a composite hydrogel formulation of pluronic acid at a concentration of
0.1-
1 0 %w/v.
The composite hydrogel formulation is typically a poloxamer. Thus, a
composition of the
present invention comprises an antimicrobial and/or anti viral mixture
consisting of:
(a) H202 at a final concentration of between 3.0 ¨ 7.0% v/v, and
(b) a poloxamer at a final concentration of 1.0%-10.0% w/v.
Typically, an antimicrobial and/or anti-viral composition as disclosed herein
comprises a
composite hydrogel formulation of component (b), which is a poloxamer, such as
pluronic
acid at a concentration of 0.1-5%w/v, such as at a concentration of at the
most 5%w/v, such
as at a concentration of between 1.0%-5.0% w/v, such as 0.1, 0.5, 1.0 or
1.5%w/v. The
composition according to the present invention in one aspect comprises a
poloxamer at a
concentration of 5.0% w/v. The poloxamer can be a mixture of poloxamers.
Component (b)
can be selected from the group consisting of pluronic acid, Pluronic0 F-127
and Poloxamer
407. In a presently preferred aspect, the poloxamer is Poloxamer 407.
An antimicrobial and/or anti-viral composition in some alternatives further
comprises a
H202 of component (a), which has a final concentration of 0.1-7%v/v, such as a
final
concentration of 0,5-3,0 %v/v. In one aspect, the H202 of component (a) has a
final
concentration of 3% v/v.
In one aspect, component (a) and component (b) are provided in a 1:1 ratio.
An antimicrobial and/or anti-viral composition in some alternatives can
further comprise
water and/or physiological saline, oils, preservatives flavors and/or
fragrances.
In one aspect, an antimicrobial and/or anti-viral composition comprises the at
least two
components:
(a) H202, and (b) a composite hydrogel formulation, comprising a poloxamer,
such as
pluronic acid, which are kept separate from each other until they are
simultaneously mixed
and applied to a biological surface and/or a biomaterial surface in situ.
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According to that aspect, an antimicrobial and/or anti-viral composition
comprises a separate
component (a), which is a composition that comprises H202 at a concentration
of at least 10-
50%v/v.
A composition according to some alternatives can further comprise an
additional
antimicrobial substance. A composition according to some alternatives can
further comprise
a bioactive substance, typically selected from the group consisting of
peptides, drugs,
bioactive ions, small molecules, radioactive molecules, and radio-opaque
molecules or any
combination thereof.
A composition according to some alternatives typically has a shelf-life of at
least 1 years at
room temperature (RT).
A composition according to some alternatives is useful for sterilizing or
sanitizing or cleaning
a biological surface and/or a biomaterial surface in situ.
Typically, one or more of the compositions described herein can be used to
clean, sterilize,
or otherwise rid the skin and/or mucosa of a subject, preferably a human, from
microbes,
including but not limited to bacteria or virus, such as Riboviria,
Coronaviridae, or
Orthocoronavirinae.
In a presently preferred aspect, one or more of the compositions described
herein are used
to clean or sterilize skin and/or mucosa from a Coronavirus, such as SARS-CoV-
2.
In consequence, aspects of the present invention relate to the application of
one or more of
the antimicrobial and/or anti-viral compositions described herein as a hand
wash, oral wash
and/or for nasal and/or sinus cleansing, so as to remove, sterilize, or
inhibit a Coronavirus,
such as SARS-CoV-2 from the skin or mucosa of a subject, preferably a human.
Aspects of the present invention also concern the use of one or more of the
compositions
described herein for cleaning and/or sanitizing a biological surface and/or a
biomaterial
surface, such as in particular an implant in situ and/or a surface in the oral
cavity and/or any
surface covered by skin or mucosa.
In some alternatives, one or more of the compositions described herein are
incorporated in a
kit, wherein the at least two components, H202 and pluronic acid, are
optionally kept
separate such that a user may mix the two components just prior to
application.
The invention consequently also relates to a method of sanitizing,
sterilizing, disinfecting
and/or decontaminating a biological surface and/or a biomaterial surface
comprising
applying the composition according to the present invention to a biological
surface and/or a
biomaterial surface, as well as a method of cleaning skin and/or mucosa of a
subject from
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microbes comprising applying the composition according to the present
invention to the skin
and/or mucosa of a subject. The microbes comprise bacteria or virus or both,
such as, but
not limited to Riboviria, Coronaviridae, Orthomyxoviridae, Caliciviridae or
Reoviridae or any
combination thereof. The microbes comprise Orthocoronavirinae, such as, but
not limitted to
Coronavirus, Rota virus, Noro virus or Influenza virus type A, B, C or D or
any combination
thereof.
DEFINITIONS and ABBREVIATIONS
Aspects of the present invention provides compositions and methods to clean
and/or sanitize
a biological surface and/or a biomaterial, such as an implant surface.
In the present context, a biological surface refers to any surface covering an
anatomical
structure and/or tissue, such as skin including palmar and plantar skin, oral
and nasal
mucosa, gastrointestinal mucosa, laryngeal, tracheal and bronchial mucosa,
vaginal
mucosa, penile mucosa, hair, nails, fasciae, membranes, synovial membranes,
dental
enamel or dental cementum. The term also encompasses a wound surface, such as
in, on
and/or surrounding, but not limited to, an ulcer, acute wound, wound from
trauma, surgical
wound, puncture wound, abrasive wound, infected wound including herpes ulcer,
papilloma,
chancre and acne, erosive wound, burn, blister, scab, leg ulcer, diabetic
ulcer and/or chronic
ulcer.
In the present context, the term "biomaterial or implant surface" typically
refers to a surface
of a medical and/or dental implant.
In the present context, the term "medical implant" includes within its scope
any device
intended to be implanted into and/or attached to the body of a vertebrate
animal, in particular
a mammal such as a human, for preservation and restoration of the function of
the body,
particularly a prosthesis of any kind, metallic and polymer-based implants in
the vascular
system or in the musculoskeletal system or in joints and bones, including for
alleviation of
pain in these structures. Non-limiting examples of medical implants are leg,
arm and hand
prosthesis, facial prosthesis, eye prosthesis, ileostomy devices, intrauterine
devices,
pacemakers, electrodes, artificial vascular structures, stents, cochlear
implants, hip-joint
prostheses, knee prostheses, elbow prostheses, finger prostheses, cochlear
prostheses, or
fixation screws.
In the present context, the term "dental implant" includes within its scope
any device
intended to be implanted into the oral cavity of a vertebrate animal, in
particular a mammal
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such as a human, for example in tooth and jaw restoration procedures. Dental
implants are
herein selected from the group consisting of: Implants, bars, bridges,
abutments, crowns,
caps, dental fillings and prosthetic parts in the oral cavity. Dental implants
may also be
denoted as dental prosthetic devices. Generally, a dental implant is composed
of one or
several implant parts. For instance, a dental implant usually comprises a
dental fixture
coupled to secondary implant parts, such as an abutment and/or a dental
restoration such as
a crown, bridge or denture. However, any device, such as a dental fixture,
intended for
implantation may alone be referred to as an implant even if other parts are to
be connected
thereto.
In a second embodiment, the term biomaterial surface includes the surface of
any medical
device or tool, disposable or not, designed to come in temporary contact with
living tissue,
such as, but not limited to, surgical instruments, electrodes, scalpels,
probes and gauges,
catheters, syringes, scissors, needle holders, contact lenses, wound
dressings, band aids,
transdermal fixing devices, and/or diagnostic tools like ultrasound devices, x-
ray machines
and/or imaging equipment, e.g. various scopes, surgical cameras, impression
materials or
intraoral scanners.
In the present context, the term peroxide is used interchangeably with
Hydrogen peroxide
and/or (H202).
A microorganism, or microbe, is a microscopic organism, which may exist in its
single-celled
form or in a colony of cells. Microorganisms include all unicellular organisms
and so are
extremely diverse. All of the Archaea and Bacteria are microorganisms
(Prokaryotes). Some
protists are related to animals and some to green plants. Many of the
multicellular organisms
are microscopic, namely micro-animals, some fungi and some algae.
An antimicrobial is an agent that kills microorganisms or stops or inhibits
their growth.
Antimicrobial medicines can be grouped according to the microorganisms they
act primarily
against. For example, antibiotics are used to treat or inhibit bacteria, and
antifungals are
used to treat or inhibit fungi. They can also be classified according to their
function. Agents
that kill microbes are microbicidal, while those that merely inhibit their
growth are called
biostatic both are included in the term" antimicrobial". The use of
antimicrobial medicines to
treat or inhibit infection is known as antimicrobial chemotherapy, while the
use of
antimicrobial medicines to prevent infection is known as antimicrobial
prophylaxis.
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A virus is a small infectious agent that replicates only inside the living
cells of an organism.
Viruses can infect all types of life forms, from animals and plants to
microorganisms,
including bacteria and archaea.
Antiviral drugs are a class of medication used specifically for treating or
inhibiting viral
infections rather than bacterial ones. Most antivirals are used for specific
viral infections,
while a broad-spectrum antiviral is effective against a wide range of viruses.
Unlike most
antibiotics, most antiviral drugs do not destroy their target pathogen;
instead they inhibit their
replication and/or development.
Antiviral drugs are one class of antimicrobials, a larger group which also
includes antibiotic
(also termed antibacterial), antifungal and antiparasitic drugs, or antiviral
drugs based on
monoclonal antibodies. Most antivirals are considered relatively harmless to
the host, and
therefore can be used to treat or inhibit infections. They should be
distinguished from
viricides, which are not medication but deactivate or destroy virus particles,
either inside or
outside the body. Natural antivirals are produced by some plants such as
eucalyptus or
Australian tea trees.
As used in the present context, the term "antimicrobial", refers to a
composition that is
effective against microbes and virus. In its broadest meaning, one or more of
the
compositions described herein are antimicrobial, e.g., antibacterial or
antiviral, a bactericide
or a viricide.
As used herein, the term "about" or "approximately" means within an acceptable
error range
for the particular value as determined by one of ordinary skill in the art,
which will depend in
part on how the value is measured or determined e.g., the limitations of the
measurement
system.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1: Gel boundaries for aqueous saline (physiological
conditions) solutions of
copolymer F-127. The filled circles are data points obtained by the tube
inversion method for the mixture. The unfilled squares are data points from
rheometric analyses. The chart clearly indicates that pluronic concentrations
below 15% w/v in saline remains fluid independent of temperature. Fluid
pluronic solutions form independent micelles, but the concentration is not
high
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enough for the pluronic micelles to assemble into a cubic gel. Thus, low
pluronic
concentrations that allow for micelle formation but stay liquid and act as
detergent may be good for tissue-friendly cleaning of biological surfaces, but
addition of other reactants that can contribute to the decontamination is
5 expected to completely disrupt the micelle formation.
Figure 2: Schematic drawing depicting the synergistic effects from
mixing pluronic with
peroxide. During the interaction with pluronic, the peroxide generates active
oxygen (ROS) degrade microbial and viral nucleic acids and membranes, and
10 kills bacteria, including anaerobes, and viruses. The peroxide
also drives
pluronic micelle dissolution that is countered by the strong tendency of
pluronic
to form micelle structures. The dynamic equilibrium between solubilized and
micelle pluronic allow for an active entrapment of dirt, organics and
contaminants into the micelle structure. The liquid hydrophilic nature of the
pluronic hydrogel also promotes easy access for the ROS to wrinkles and
crevices, unhindered by foaming. Moreover, the pluronic hydrogel moisture the
skin and the oxygen released from the peroxide helps the wound to heal. The
ROS also has the ability to clean and reactivate (make the surface
hydrophilic)
titanium, one of the most widely used metal in medical and dental implants.
The
effect of ROS alone is too brief to have a significant impact on these
processes
and would not remove the contaminants or provide moisture. Pluronic alone for
stable micelles that is far less effective in contaminant entrapment and do
not
kill microbes or degrade viral nucleic acids. Mixed together in the right
concentration pluronic micelle formation is more dynamic, moistening and
oxygenation is optimized, and the peroxide action is prolonged and increased
and kept at the surface where it is needed.
Figure 3: Titanium surfaces contaminated with S. Epidermidis
bacteria was cleaned with
growth medium (BHI, Negative control), H202 5% v/v + f-127 1% w/v (Test 2),
H202 5% v/v + f-127 7% w/v (Test 4), Chlorhexidine 0,2% w/v + f-127 7% w/v
(Test 5) or Ethanol 75% v/v + f-127 1% w/v. The negative control did not
remove the bacteria, nor was the bacteria destroyed. The peroxide + pluronic
acid mix killed all bacteria, dissolved the biofilm and removed the debris
almost
completely (Tests 2 & 4). Test 4 was slightly, but not statistically
significant,
more effective than Test 2. Chlorhexidine (Test 5) and Ethanol (Test 6) did
kill
most of the bacteria but did not remove any debris from the surface, leaving
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the surfaces heavily contaminated. Surfaces visualized after cleaning in a
scanning electron microscope. Scale bar is 20 micrometres.
Figure 4: Titanium surfaces contaminated with S. Epidermidis
bacteria was cleaned with
A) saline (Negative control), B) Chlorhexidine 0,2% w/v, or C) H202 3% v/v +
f-127 pluronic Acid 5% w/v. After cleaning the surfaces were stained with
fluorescent dyes, green for living cells and red for dead cells. The negative
control (saline) did not remove any of the bacteria, nor was the bacteria
destroyed. The chlorhexidine killed all bacteria but left them to contaminate
the
surface. The hydrogen peroxide + pluronic acid mix killed all bacteria,
dissolved
the biofilm and removed the debris almost completely Surfaces visualized in a
confocal microscope after cleaning and staining.
Figure 5: Regrowth of S. Epidermidis bacteria, harbouring the
luciferase gene making
them fluorescent, on sanitized titanium surfaces. The results show that D)
water
with detergent (SDS, 0,1%), E) water with 5% pluronic acid and F) saline had
minimal sanitizing effect, as regrowth of the biofilm occurred within 3-4
hours
after cleaning. Chlorhexidine, 0,2%, on the other hand killed all bacteria
with
no regrowth observed although the dead biofilm stuck and remained on the
surface (see figure 3 and 4). Hydrogen peroxide, 5% v/v, alone (A) cleaned the
surface well as seen by a delay of about 13 hours before the biofilm restored
itself. However, hydrogen peroxide 3% v/v combined with 5% pluronic acid in
water cleaned the surface significantly better, delaying regrowth with more
than
15 hours.
Figure 6: Left and right thumbs were sanitized four times daily for
five consecutive days
with a mix of A) pluronic acid (5% w/v) and hydrogen peroxide (3% v/v) or B)
Antibac PharmaTM containing ethanol and propan-2-ol respectively. After the
sanitizing period both fingers were stained with iron oxide to visualize
fissures
and cracks. Fissures and cracks are easily visible as brown striated stains on
the Antibac PharmaTM treated thumb, whereas the pluronic-peroxide
formulation caused no harm to the skin of the left finger.
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Figure 7: Fingers were marked with a line of permanent ink from a
laboratory marker that
was subsequently washed off with various sanitizing/decontaminating solutions
to visualize their ability to remove contaminants from the skin. Finger A) was
washed only with water. Finger B) was cleaned with warm water and soap.
Finger C) was cleaned with 0,2% chlorhexidine and finger D) was rinsed with
PyrispetTM (0,1% cetyl-pyridinium chloride). Finger E) was cleaned with
Antibac
PharmaTM (Alcohol based sanitizer), finger F) was cleaned with bleach (4%
Sodium hypochlorite). Fingers G) and H) were rinsed with hydrogen peroxide
(1% and 5% v/v in water respectively). Finger I) was washed in a solution of
pluronic acid in water (5% w/v). Finger J) was sanitized with a mix of
pluronic
acid (5% w/v) and hydrogen peroxide (1% v/v). The results show that bleach
and hydrogen peroxide is effective in removing the ink stain, but that the
most
efficient cleaning is obtained by the combination of pluronic acid and
hydrogen
peroxide.
DETAILED DESCRIPTION
There has been a long felt need in community for the presently described
compositions,
which effectively clean, disinfect and/or sanitize a biological surface and/or
a biomaterial
surface. e.g., including but not limited to skin or mucosa, such as a surface
in the oro-
laryngeal or nasal cavity. Any one or more of the compositions described
herein are useful
for the rapid and effective treatment or inhibition of bacteria or virus or
both essentially
without leaving contaminating material residues.
The presently described compositions are water soluble and easy to rinse off,
tissue-friendly
non-ionic surfactant. These compositions comprise a non-toxic formulation of
well-studied
active ingredients in clinical use, which is particularly suitable for
injectable, oral and/or
cutaneous applications. The herein for the first time described composition is
proven to be
non-sensitizing and non-irritating in clinical tests. The compositions
described herein are
compatible with most other therapeutic agents useful against biofouling and
inflammation.
The compositions described herein have a liquid state at room temperature that
allows
trouble-free mixing and application. The compositions have an easy flowing
liquid
consistency with a surfactant effect that allows the compositions to reach
difficult places
when applied into narrow crevices, defects and/or folds on skin and/or mucosa.
Without being bound to a particular theory or mechanism of action, it is
contemplated that he
compositions described herein mimic the natural release of reactive oxygen
species (ROS)
from peroxide produced by human cells. The charge from the reactive oxygen
destroys
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microbial membranes and the oxygen itself is also toxic to anaerobic bacteria.
The human
cells themselves are protected against ROS by enzymes in their cell membrane
and the
local tissue can benefit from the increase in oxygen. Microbes have no such
protection, nor
can they develop resistance because of fundamental differences in their cell-
membrane
design. Thus, the composition can effectively dissolve biofilm, debris and
mineral deposits,
as well as, dissolve extracellular organics at the application site.
Through the active oxygen released from the liquid hydrogel, the use of the
herein presented
compositions also remove carbon contamination from a titanium containing
implant
surface and reactivate the titanium dioxide layer of the implant. This process
re-establishes
the original charge and hydrophilicity of the implant, restoring its optimal
biological surface
properties. This is a factor for further survival, or even successful
reintegration, of said
treated implant. The present compositions provide an advanced micelle forming
gel
formulation that works in synergy with natural occurring oxygen to break down
and remove
biofouling, eliminate microbes, keep tissue and implant moist and reactivate
titanium implant
surfaces.
The hydrogel component of the compositions and the active oxygen work in
synergy to avoid
foaming from oxygen release and to keep activated oxygen in place at the
surface for a
prolonged biological and chemical effect. The use of any one or more of the
compositions
set forth herein provides moisture and allows the charged oxygen to work
without risk of
drying out skin, tissue and/or implant surfaces, during which the active
oxygen eradicates
microbes that are then suspended and entrapped inside the micelle-forming
hydrogel.
Organic contaminants are in turn denatured by the strong detergent effect,
broken down by
the active oxygen and dissolved and entrapped in the hydrogel. Both hydrogel
and oxygen
reduce inflammation and support tissue health. The active oxygen released in
turn
strengthens the cellular defence network. In synergy, the gel and the active
oxygen both
removes contaminants, acts as an antimicrobial and viricidal agent and
reactivates a
titanium implant surface. The interaction between the pluronic micelle
formation and
peroxide potentiates micelle formation and increases the cleaning effect
significantly.
The presently described compositions provide a novel formula of a
biocompatible hydrogel-
peroxide combination with strong, antimicrobial, viricidal and non-ionic
detergent properties
with improved micelle dynamics for solubilization and entrapment of debris and
microbes for
effectively cleaning, sanitizing, sterilizing and/or debriding a biological
surface and/or a
biomaterial surface in situ. It is easily rinsed off with a towel, wipe or by
water, but it can also
be left to air-dry and will completely decompose to water, oxygen and carbon
dioxide.
The presently disclosed compositions provide a novel and improved approach to
cleaning,
sanitizing, sterilizing and/or disinfecting skin, mucosa and/or implant
surfaces. In particular
alternatives, for example, any one or more of the compositions described
herein are
incorporated into a mouth wash and/or nasal rinse and these formulations can
be used to
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prevent, treat, inhibit, or ameliorate, an oral and/ or nasal disease (e.g.,
dental caries,
periodontitis, gingivitis, mucositis, peri-implantitis, sinusitis and/or
rhinitis). In additional
alternatives, said mouth rinses and/or nasal rinses can be used in methods to
inhibit
bacterial or viral infections, such as SARS-CoV-2 in the oral or nasal mucosa
of a subject,
such as a human.
The desired formulations set forth herein are based on the combination of
hydrogen
peroxide (H202) and pluronic acid in such a concentration that the resulting
composition is in
a watery liquid form at physiological temperatures. The H202 component of the
composition
can either be in the form of a concentrate (at a concentration of at least 10-
50%v/v.) in a
separate vial for mixing immediately before use, or provided as an emulsion or
dissolved
directly into a hydrogel, said hydrogel at least partly consisting of pluronic
acid and water
and/or physiological saline, with a typical final concentration of 0.5 ¨ 7%.
The pluronic
component itself can be any one or a combination of the pluronic acids, e.g.
the F-127
variety. The concentration of pluronic acid is typically 0.1-10% w/v, such as
0.1-7% w/v, such
as 0.1-2.5% w/v. That is, the concentration of pluronic acid in any one or
more of the
compositions described herein can be at least or equal to 0.1%, 0.5%, 1.0%,
1.5%, 2.0%,
2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%,
9.0%, or
10% w/v or a percentage w/v that is within a range defined by any two of the
aforementioned
percentages.
Pluronic-acid works both as solubilizer and detergent in the composition
disclosed herein, as
well as a moisturizer. In the presence of peroxide, the hydrogel formulation
establishes a
dynamic micelle forming solution. This dynamic state facilitates efficient
solubilization and
entrapment of particles, microbes and pollutants during the cleaning procedure
(see e.g.
Figure 2).
The present innovation is based on a synergetic effect between pluronic acid
and peroxide.
Pluronic acid has an ability to form micelles. This ability usually increases
with increasing
temperature and is shifted toward a gel state at physiological conditions
(such as at >20
degrees Celsius). The peroxide addition allows the pluronic acid to stay in
the liquid state
even at physiological temperature.
When mixed with hydrogen peroxide, the present inventors for the first time
disclose that the
micelles are more dynamic and less stable and in a "dynamic" equilibrium with
the peroxide
radical activity even under high temperature. In effect, this means that in
the presence of
peroxide, the micelle structure is dissolved and reforms constantly also when
the gel is
applied onto human tissue, skin and/or mucosa. This effect keeps the hydrogel
liquid also at
high temperatures and increases the detergent, denaturation and entrapment
effect of the
pluronic acid significantly.
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Combined with the effect of hydrogen peroxide to release free oxygen radicals
on viral
particles, microbes and necrotic tissue, the micelle transitions dissolve and
entrap organic
contamination that are then removed when the gel dries off, is wiped off, or
washed off.
5 Desirably, the addition of hydrogen peroxide to the pluronic acid in the
compositions
described herein increases the temperature at when gelation occurs. e.g., that
the pluronic
gel, containing low concentrations of peroxide, is liquid at room temperate
and thus can be
applied through a syringe needle or from a dispenser bottle without clogging
the nozzle. This
is not possible with pluronic acid alone because it starts forming a stable
"packed micelle"
10 gel already at room temperature, even at low concentrations when in narrow
compartments
and/or at the "vapor front" at the nozzle of the dispenserõ thus is very hard
to squeeze
through a narrow tip of a syringe, or a pump applicator from a dispenser
bottle. pluronic gel
for wound care is therefore sold as gel in a box or a tube. The increased
effect from the
combination of peroxide and pluronic acid was unexpected and surprising.
The liquid formulation of the pluronic hydrogel in combination with peroxide
also assists
during application. It enables the cleaning and/or sanitizing composition to
reach folds,
wrinkles, crevices, fissures, narrow spaces and/or undercuts that a pluronic
gel alone cannot
reach because of its gel forming nature making it viscous at physiological
temperatures.
Thus, it is more efficient in cleaning rough (implant) surfaces, narrow spaces
such as folds,
fissures and wrinkles on skin and mucosa and between teeth.
Compositions
Aspects of the present invention relate to novel antimicrobial and/or anti-
viral compositions,
which can be used for cleaning, sanitizing, sterilizing, disinfecting and/or
decontaminating a
biological surface and/or a biomaterial surface in situ. In some alternatives,
the
aforementioned compositions comprise two components:
a. H202 at a final concentration of between 0.1 - 7%v/v, and
b. a composite hydrogel formulation of pluronic acid at a concentration of
0.1 - 10%w/v.
In some of the aforementioned compositions, the final concentration of H202 is
at least or
equal to 0.1%, 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%,
5.5%, 6.0%,
6.5%, or 7.0% w/v or a percentage w/v that is within a range defined by any
two of the
aforementioned percentages. In some of the aforementioned compositions, the
final
concentration of pluronic acid is at least or equal to 0.1%, 0.5%, 1.0%, 1.5%,
2.0%, 2.5%,
3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%,
or 10%
w/v or a percentage w/v that is within a range defined by any two of the
aforementioned
percentages.
Preferably, said compositions are formulated so that they remain a liquid at
physiological
temperatures, such as at a temperature of at the most 40 C, such as at a
temperature
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between 20-40 C, such as at 37 C e.g., 20, 22, 24, 26, 28, 30, 32, 34, 36, 38,
or 40 C or at
a temperature that is within a range defined by any two of the aforementioned
temperatures.
Some of the presently disclosed compositions are characterized in that they
comprise a low
concentration of pluronic acid, which allows the composition to be in a liquid
state in high
temperature instead of in a gel-state, which a desirable feature for it to be
usable for
cleaning, sanitizing, sterilizing, disinfecting and/or decontaminating a
biological surface
and/or a biomaterial surface in situ. In particular, the liquid state of the
hydrogel is desired
when the composition is incorporated into a hand sanitizer, hand wash, oral
wash and/or for
nasal and/or sinus cleansing solution, in particular for washing virus off of
skin and mucosa.
The presently disclosed compositions comprise the at least two components (a)
and (b) in
such a ratio that the composition is in a liquid state at physiological
temperatures instead of
in a more viscous or gel-like state. Typical ratios of concentrations between
component (a)
and component (b) are approximately 1:1 (concentration of H202: concentration
of pluronic
acid). In general, the higher the concentration of the pluronic acid, the
higher the
concentration of the H202 is needed to keep the composition in a liquid state
at temperatures
of between 25-40 C. However, too high concentrations of peroxide will destroy
the pluronic
acid amphiphilic properties and disrupt micelle formation, rendering it
useless as a detergent
and/or a desatu rating agent.
In one alternative of an antimicrobial and/or anti-viral composition according
to the present
invention, the composite hydrogel formulation of component (b) comprises
pluronic acid at a
concentration of 0.1-10%w/v, such as at a concentration of 10% w/v, such as of
0.1, 0.5, 1,
1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9 or 9.5 %w/v or
an amount that is
within a range defined by any two of the aforementioned concentrations.
In another alternative of an antimicrobial and/or anti-viral composition
according to the
present invention, the composite hydrogel formulation of component (b)
comprises pluronic
acid at a concentration of at the most 10% w/v, such as at the most 0.1, 0.5,
1, 1.5, 2, 2.5, 3,
3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9 or 9.5 %w/v or an amount that
is within a range
defined by any two of the aforementioned concentrations.
An antimicrobial and/or anti-viral composition according to the present
invention can be a
composition wherein the H202 of component (a) has a final concentration of 0.1-
7%v/v, such
as 0.5-3%v/v, such as 0.1-5 /0v/v. In one embodiment, the H202 of component
(a) has a final
concentration of no more than 7%v/v, such as 0.1-7`)/ov/v, such as 1, 2, 3, 4,
5, 6 or 7%v/v.
An antimicrobial and/or anti-viral composition according to the present
invention can further
comprise water and/or physiological saline.
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The two components of the antimicrobial and/or anti-viral composition
according to the
present invention can be in one solution or the at least two components can be
kept
separate from each other such that they can be simultaneously mixed and
applied to a
biological surface and/or a biomaterial surface in situ.
In an antimicrobial and/or anti-viral composition according to the present
invention, wherein
the components are kept separate from each other before application, the
separate
component (a) can be a composition that comprises H202 at a concentration of
at least 10-
50%v/v, such as at the most 10, 20, 30, 40 or 50% v/v. In one alternative, a
composition of
the present invention comprises H202 at a concentration of 30%v/v.
Emulsifier(s) and/or viscosity modifier(s)
In some alternatives, the antimicrobial and/or anti-viral composition
according to the present
invention further comprises one or more emulsifier(s) and/or viscosity
modifier(s). Said
emulsifier and/or viscosity modifier may be selected from the group consisting
of glycerine,
glycols, polyethylene glycols (PEG), polyoxyethylene polyoxypropylene block
copolymer
(pluronic polyols), polyglycol alginate (PGA), CMC (carboxyl methyl
cellulose), glycerol, Aloe
Vera gel, alginate, hyaluronic acid (HA) and chitosan or any combination
thereof.
The antimicrobial and/or anti-viral composition according to the present
invention may also
comprise one or more detergent(s) selected from the group consisting of SDS
(sodium
dodecyl sulphate), sodium stannate, sodium pyrophosphate, oxine and SLS
(sodium lauryl
sulphate) or any combination thereof.
The antimicrobial and/or anti-viral composition according to the invention may
further
comprise one or more fragrance or flavouring oil(s), such as, but not limited
to perfumes and
oils of spearmint, peppermint, wintergreen, sassafras, clove, sage,
eucalyptus, marjoram,
cinnamon and methyl salicylate or menthol or any combination thereof.
The antimicrobial and/or anti-viral composition according to the invention may
further
comprise one or more weak acidic buffers.
The antimicrobial and/or anti-viral composition according to the invention may
further
comprise one or more stabilizers such as, but not limited to organophosphates,
carboxylate
salts, sodium pyrophosphate, sodium phytate, colloidal stannate or sodium
citrate or any
combination thereof.
Bioactive substance
Alternatively, or in addition, one or more of the compositions according to
the present
invention can comprise a bioactive substance, typically selected from the
group consisting of
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EMD, peptides, drugs, bio active ions, small molecules, radioactive molecules,
antimicrobial
molecules and radio-opaque molecules or any combination thereof.
Cleaning components and antimicrobial substances
What is more, one or more of the compositions according to the present
invention can also
comprise an additional antimicrobial substance and/or cleaning component.
In the present context, an additional antimicrobial substance provided in one
or more of the
compositions according to the present invention can be selected from the non-
exclusive list
consisting of amoxicillin, doxycycline, cephalexin, ciprofloxacin,
clindamycin, metronidazole,
azithromycin, sulfamethoxazole and trimethoprim or any combination thereof.
In one aspect, a further antimicrobial substance provided in one or more of
the compositions
according to the present invention is an alcohol, tetracycline, doxycycline,
macrolides,
penicillin (stabilized), chlorhexidine, chloramines or mixtures thereof.
In one aspect, one or more of the compositions according to the present
invention comprises
an additional anti-viral substance.
In one aspect, one or more of the compositions according to the present
invention comprises
an additional anti-inflammatory, antiphlogistic, coagulating, anesthetic
and/or pain-killing
agent or substance.
In one aspect, one or more of the compositions according to the present
invention comprises
one or more of prophylactic and/or anti-tooth-decay agents, such as, but not
limited to,
hydrogen fluoride, sodium fluoride, or stannous fluoride or any combination
thereof.
Shelf-life of at least 1 years in room temperature (RT)
A composition according to the present invention in one aspect has a shelf-
life of at least 1
years at room temperature (RT).
A kit
Aspects of the present invention also relate to a kit comprising a composition
described
herein, wherein said kit comprises at least two containers comprising said
separated
components (a) and (b), respectively, a syringe and a vial, a connector
device, an applicator
tip and an instruction leaflet and, optionally a mixing device and a cleaning
tool, such as but
not limited to a brush. Said kit can provide the two components (a) and (b) in
a two-chamber
syringe, in which case the kit further can comprise an instruction leaflet, a
mixing device, an
applicator tip and a cleaning tool, such as but not limited to a brush and/or
a wipe.
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An antimicrobial and/or anti-viral composition according to the present
invention can be
mixed before application and eventual storage or stored separately and mixed
directly or
shortly before and/or at the time of application. The application therefore,
in another aspect
is directed to a kit comprising a first container comprising component (a), a
second container
comprising component (b), and optionally at least one more (third or forth
etc.) container
comprising a component (c), (d), (e) etc.), which can e.g. comprise paper
and/or cotton
wipes, such as but not limited to wet-wipes, microparticles and/or a mesh-
forming substance
and/or a bioactive substance and/or a cleaning component and/or a further
antimicrobial
and/or anti-viral substance.
Optionally such a kit may also comprise instructions for the preparation of
the composition of
the invention. The kit may also comprise one or more device(s) for the
application of the
composition to a subject. Such a device may e.g. be a dispenser bottle, a
blister pack, a
double blister pack, a syringe and/or an implant cleaning and/or sanitizing
tool for cleaning
and/or sanitizing an implant, such as in the oral cavity.
A kit of the invention may also comprise one or more of the compositions
described herein in
one or more container(s) and an implant cleaning and/or sanitizing tool for
cleaning and/or
decontamination of an implant in the oral cavity.
In a presently preferred aspect, a kit comprising a composition according to
the present
invention typically provides the two components (a) and (b) in a two-chamber
device that
allows for easy mixing of the components prior to and/or or during
application. Typically,
such a device can be a two-chamber syringe, a two-chamber pump-action
dispenser bottle a
double blister (blister in blister) pack, or a wet-wipe blister containing a
separate blister,
containing peroxide, to be broken by force prior to application.
The kit can further comprise a container, such as a blister-pack and/or
tissues, such as
sanitizing wipes for applying the composition according to the present
invention.
Uses
The presently disclosed composition is intended for use in cleaning,
sanitizing, disinfecting
and/or sterilizing a biological surface and/or a biomaterial surface in situ.
In one aspect of the invention, the antimicrobial and/or anti-viral
composition according the
present invention is for use in sterilizing, disinfecting and/or sanitizing a
biological surface
and/or a biomaterial surface in situ.
Thus, an antimicrobial and/or anti-viral composition according to the present
invention is
typically used for cleaning, sterilizing, disinfecting and/or sanitizing skin
and/or mucosa from
microbes.
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In particular, the microbes to be killed or removed by the composition
according to the
present invention are selected from the group consisting of bacteria and
virus, such as
selected from the non-exclusive group consisting of Riboviria, in particular
Coronaviridae
(e.g., Sars-Cov-2), or Orthocoronavirinae.
5
An antimicrobial and/or anti-viral composition according to the present
invention is in
particular well-suited for killing and/or removing Coronaviruses, such as from
skin and/or
mucosa, including from hands, face, or oral or nasal cavities.
10 The present invention thus in a presently preferred aspect also relates to
the application of
an antimicrobial and/or anti-viral composition according to the present
invention as a hand
wash, oral wash, tooth wash, for nasal and/or sinus cleansing, and/or for
washing virus off
skin and mucosa.
15 The present invention thus in a presently preferred aspect also relates to
the application of
an antimicrobial and/or anti-viral composition according to the present
invention as a hand
sanitizer, mouth wash, sinus rinse, nasal rinse and/or sanitizing wipes.
The presently disclosed composition is also useful for application in pen-
implant defects, and
20 the formulation may be tailored to fit with various clinical procedures,
such as but not limited
to treating and preventing oral infections , for maintaining oral and/or nasal
health and post-
operative follow-up administrations to skin, mucosa and/or oro-laryngeal
and/or nasal
cavities.
The presently disclosed composition can also be used for other oral
procedures, such as
during surgical cleaning of periodontal defects, for preparation before
regenerative
procedures, in periodontal maintenance treatment, in periodontitis prophylaxis
(by dental
hygienists), as well as in endodontics, both in root-canal procedures and in
apical surgery.
What is more, the presently disclosed composition can further be used for
cleaning and/or
debriding outside the oral cavity, such as, but not limited to in orthopaedic
revision surgery,
sanitizing of transdermal devices, in dermal wound care for cleaning of acute
wounds and/or
in cleaning of chronic ulcers and burns.
An antimicrobial and/or anti-viral composition according to the present
invention can typically
be employed for use in the treatment and/or prevention of peri-implantitis,
gingivitis and/or
mucositis, pen-implant mucositis and/or periodontitis or for the sanitizing of
the oral cavity
against contagious disease or prior to oral surgery procedures.
Periimplantitis is a typical complication related to orodental rehabilitation
through the use of
implants, e.g., a pen-implant disease, which is well-known to the person
skilled in the art as
an inflammatory reaction to oral microbes in which there is an accompanied
loss of the bony
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support of the implant. The aetiology of the disease is conditioned by the
status of the tissue
surrounding the implant, implant design, degree of roughness, the poor
alignment of implant
components, external morphology and excessive mechanical load.
The presently described antimicrobial and/or anti-viral composition offers
several
approaches for an effective and rapid cleaning of an implant and/or for
sanitizing or
decontaminate a tissue surface in the oral cavity essentially without damaging
of the delicate
structure or of the implant surface and/or the tissue surface itself, and
essentially without
leaving contaminating material residues on the treated surface.
The invention therefore in one aspect is directed to the antimicrobial and/or
anti-viral
composition as defined herein and/or the kit for preparing the composition of
the invention as
defined herein, for use as a medical device or a medicament.
Thus, the present invention relates to the use of an antimicrobial and/or anti-
viral
composition according to the present invention for cleaning and/or sanitizing
and/or
decontaminate an implant in the oral cavity, such as an implant in situ, a
tissue surface in the
oral cavity, such as an outer surface of a tissue in the oral cavity, a
surgically exposed
surface in the oral cavity, a wound in the oral cavity, such as a wound
resulting from
periimplantitis or a surgical wound, a periodontal defect and/or periodontal
wound, and/or an
oral hard tissue defect.
Implants
The invention also relates to the use of the antimicrobial and/or anti-viral
composition as
defined herein and/or the kit for preparing the composition of the invention
as defined herein,
for the preparation of a medicament and/or a pharmaceutical and/or cosmetic
composition,
for cleaning and/or decontaminating an implant in the oral cavity, such as an
implant in situ,
a hard surface in the oral cavity, such as an outer surface of a hard
tissue in the oral cavity, a surgically exposed hard surface in the oral
cavity, a wound in the
oral cavity, such as a wound resulting from periimplantitis or a surgical
wound, a periodontal
defect and/or periodontal wound, and/or an oral hard tissue defect.
The invention is also directed to the antimicrobial and/or anti-viral
composition as defined
herein or the kit for preparing the composition of the invention as defined
herein for use
cleaning, sanitizing, disinfecting, sterilizing and/or debriding an implant in
the oral cavity,
such as an implant in situ, a hard surface in the oral cavity, such as an
outer surface of a
hard tissue in the oral cavity, a surgically exposed hard surface in the oral
cavity, a wound in
the oral cavity, such as a wound resulting from periimplantitis or a surgical
wound, a
periodontal defect and/or periodontal wound, and/or an oral hard tissue
defect.
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Oro-laryngeal and nasal medical applications
In dentistry and otorhinolaryngology, nasal and mouth rinses are used pre- and
post-surgery
to lower the microbial burden during a procedure, or to treat infections. The
infection of oro-
larynx and nasal mucosa leads to formation of mucus that can fill up sinuses
and cause
nasal and sinus congestion and microbe accumulation on tongue, tonsils, teeth
and gums.
The invention is also directed to the antimicrobial and/or anti-viral
composition as defined
herein for use as mouth wash, nasal rinse and/or sinus rinse for the
disinfection and cleaning
of oral, laryngeal and/or nasal anatomical structures and/or surfaces.
Microorganisms
An antimicrobial and/or anti-viral composition according to the present
invention is in general
intended for use in cleaning, disinfecting, sanitizing and/or decontaminating
a biological
surface and/or a biomaterial surface in situ, e.g. for use in removal of
virus, microbes,
including but not limited to bacteria, yeasts, and bacterial spores, and dirt
from such a
biological surface and/or a biomaterial surface in situ.
Biofilms that can be prevented, eliminated and/or treated by the composition
of the present
disclosure include, but are not limited to, biofilms present within the oral
cavity, e.g., on the
surface of teeth, on the surface of mucosal/soft-tissues such as
gingivae/periodontium and
inside a tooth canal (e.g. the endodontic canal).
In certain embodiments, biofilms that can be prevented, eliminated and/or
treated by the
composition of the present disclosure include biofilms on the urinary tract,
lung,
gastrointestinal tract, on and/or within chronic wounds, and present on the
surface (e.g.,
implants) and within medical devices and medical lines, e.g., catheters,
medical instruments
or medical tubing.
The composition of the present disclosure can be used to reduce the growth
and/or inhibit
the viability of one or more microorganisms, e.g., bacteria in a biofilm. For
example, and not
by way of limitation, the bacteria, which can be inhibited can include
Streptococcus mutctns
(S. mutctns), Streptococcus sobrinus, Streptococcus sctnguis (sctnguinis),
Streptococcus
gordonii, Streptococcus omlis, Streptococcus mitis, Actinomyces odontolyticus,
Actinomyces
viscosus, Aggregcttibctcter ctctinomycetemcomitctns, lctctobctcillus spp.,
Porphyromoncts
gin givctlis, Prevotellct intermedia, Bacteroides forsythus, Treponema
denticola,
Fusobacterium nucleatum, Campylobacter rectus, Eikenella corrodens,
Veillonella spp.,
Micromonas micros, Porphyromonas cangingivalis, Haemophilus
actinomycetemcomitans
Actinomyces spp., Bacillus spp., Mycobacterium spp., Fusobacterium spp.,
Streptococcus
spp., Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalectiae,
Proteus
mirabilis, Elebsiella pneumoniae, Acinetobacter spp., Enterococcus spp.,
Prevotella spp.,
Porphyromonas spp., Clostridium spp., Stenotrophomonas maltophilia, P.
cangingivalis,
Candida albicans, Escherichia coil and/or Pseudomonas aeruginosa. In certain
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embodiments, the bacteria are S. mutans, which is present within biofilms
found in the oral
cavity, e.g., on the surface of teeth.
The microorganisms most commonly associated with implant failure are
spirochetes and
mobile forms of Gram-negative anaerobes. Diagnosis can be based on changes of
colour in
the gum, bleeding and probing depth of pen-implant pockets, suppuration, x-ray
and gradual
loss of bone height around the tooth. The antibiotic therapy proven to be most
efficacious in
the antibiogram has so far been the association of amoxycillin and clavulanic
acid. In
addition to bacterial infections, microbial infections in the oral cavity can
of course also
include fungal and/or viral infections.
An antimicrobial and/or anti-viral composition according to the present
invention is effective
for killing bacteria, fungus and/or virus.
Typically, a composition according to the present invention is for use in
cleaning skin and/or
mucosa from virus such as, but not limited to, Riboviria, such as
Coronaviridae, such as
Orthocoronavirinae and Orthomyxoviridae such as Influenza A, B, C and D virus,
Arbo virus
and lsavirus, and such as Rotavirus, Noro virus, Adenovirus, Papillomavirus,
Herpes virus,
Hepatitis virus, Small Pox virus, Parvo virus, Ebola virus, Measles virus or
Rabies virus.
In a presently preferred aspect, a composition according to the present
invention is for use in
cleaning skin and/or mucosa from Coronavirus or Influenza virus.
What is more, the composition described herein is antimicrobial, without
causing microbial
resistance, as well as anti-viral.
In consequence, the present invention relates to a method for cleaning,
sanitizing, treating
and /or preventing contagious diseases, infections, gingivitis and/or
mucositis, pen-implant
mucositis, peri-implantitis, periodontitis, tooth decay, and/or sinusitis and
rhinitis, comprising
cleaning of a biological surface and/or a biomaterial surface in situ by
applying a
composition according to the present invention to said fouled, filmed and/or
contaminated
structure, tissue or surface.
EXAMPLES
The following Examples have been included to provide guidance to one of
ordinary skill in
the art for practicing representative embodiments of the presently disclosed
subject matter.
Considering the present invention and the general level of skill in the art,
those of skill can
appreciate that the following Examples are intended to be exemplary only and
that
numerous changes, modifications, and alterations can be employed without
departing from
the scope of the presently disclosed subject matter.
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Example 1
Analysis of micelle formation of pluronic in presence of peroxide
Pluronic F-127 added to an aqueous solution can change its thickness
depending on the
concentration and temperature. F-127 is a non-ionic, surfactant polyol with a
molecular weight
of 12500 Daltons.
As can be seen in figure 1, gel boundaries for aqueous saline (physiological
conditions)
solutions of copolymer F-127. The filled circles are data points obtained by
the tube inversion
method for the mixture. The unfilled squares are data points from rheometric
analyses. The
chart clearly indicates that pluronic concentrations below 15% w/v in saline
remains fluid
independent of temperature. Fluid pluronic solutions form independent
micelles, but the
concentration is not high enough for the pluronic micelles to assemble into a
cubic gel. Thus,
low pluronic concentrations that allow for micelle formation but stay liquid
and act as detergent
may be good for tissue-friendly cleaning of biological surfaces, but addition
of other potent
reactants that can contribute to the decontamination is expected to completely
disrupt the
micelle formation and thus abolish the wanted detergent and denaturing
effects.
Adding Peroxide to the Pluronic f-127 gel
In order to test if micelle formation (as visualised by ability to foaming and
dissolve oil) still
could be obtained when mixing low concentration of Pluronic f-127 in water
with various
antimicrobial agents (see example 3), hydrogen peroxide, in a wide range of
peroxide
concentrations, was tested (Table 1).
The technique used for making aqueous poloxamer solution is simple. Weighed
amount of the
f-127 is slowly added to a known weight of cold water (less than 10 C) with
careful stirring.
The stirring rate should be controlled so as to maintain a slight vortex in
the liquid. Too rapid
a stirring rate will cause aeration and the formation of foam.
Sample Pluronic F-127(gr) H20 (ml) 50% H202(m1)
0 2.5 50.00 0.00 (0.0%)
1 2.5 49.90 0.10 (0.1%)
2 2.5 49.50 0.50 (0.5%)
3 2.5 49.00 1.00 (1.0%)
4 2.5 48.50 1.50 (1.5%)
5 2.5 47.00 3.00 (3.0%)
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6 2.5 44.00 6.00 (6.0%)
7 2.5 38.00 12.00 (12.0%)
Table 1: Compositions of suspensions containing 5% pluronic Acid F-127 (Zigma
Aldrich) in
water and a range of Hydrogen Peroxide (Sigma Aldrich). After dissolving the f-
127 in cold
water, the right amount of hydrogen peroxide was added, mixing was done by
inverting tubes
5 carefully to avoid foaming, and the solutions were left on the bench at room
temperature for
10 minutes. When all the polymer has been added, stirring can be continued
(while keeping
the solution cool) until a clear solution is formed or the container can be
placed in a refrigerator
and left undisturbed for several hours, at which time solution is complete.
The H202 was mixed
in by slight stirring for a few seconds when the experiment started.
Sample Foaming (0-3) Oil absorption per % of H202
50 ml (droplets)
0 3 7 0.00
1 2 6 0.1%
2 3 12 0.5%
3 3 11 1.0%
4 3 7 1.5%
5 2 5 3.0%
6 1 2 6.0%
7 1 0 12.0%
Table 2: After incubation all the solutions were still liquid (no gel
formation as expected) and
were vortexed and the ability to form foam (as a simple measurement of
surfactant effect) was
scored on a scale from 0 (no foam) to three (much foam). As expected, sample 0
scored
maximum, and addition of hydrogen peroxide reduced foaming at low and high
concentration.
Unexpectedly there were no linearity in the reduction of foaming. In fact,
samples 2 trough 4
scored as high as the control, indicating that micelle formation and
surfactant effect were
preserved in these samples. The samples were then tested on how many oil
droplets (mineral
oil stained with oil red (Sigma Aldrich)) from a needle point the solutions
could absorbed before
getting turbid. Turbidity is a sign of macro-emulsion, a stage where oil
droplets become so big
that they disperse light. The positive control, Sample 0, absorbed 7 oil
droplets before getting
turbid. The negative control, sample 7, turned turbid with the first droplet.
The expected
linearity between these extremes was however not observed. Surprisingly,
sample 2 (0.5%
Peroxide) and 3 (1.0% peroxide) actually absorbed almost twice as many
droplets than the
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positive control before turbidity was observed. This indicates that Pluronic f-
127 micelle
formation at low concentrations (=liquid solutions) actually is more
efficient, and dynamic, in
presence of low concentrations of hydrogen peroxide in the range of 0,5 ¨ 1,5%
volume by
volume (in a 5% w/v solution of f-127).
Example 2
Test of biocompatibility of pluronic acid combined with peroxide
Test procedure:
The biocompatibility test was performed according to ISO 10993-5:2009
Biological
evaluation of medical devices Part 5: Tests for in vitro cytotoxicity.
Colorimetric assay such MTT, WST-1 or LDH was not used as the peroxide
suspension
degrade the indicator colour used in these assays and thus, they cannot be
used. Instead
radioactive labelling with [3H] thymidine incorporation was used to analyse
the cytotoxicity of
the pluronic-peroxide solution on normal human dermal fibroblast cells (NHDF)
(Lonza
Walkersville, Inc. Walkersville, MD, USA).
Due the viscosity of the tested hydrocolloid gels (SilvaSorb0 Gel, Medline
Industries,
Munedelein, IL) and the pluronic-Peroxide gels (20%Pluronic f-127 in water
with 3%
Hydrogen Peroxide), the test samples could not be diluted into the cell
culture medium. Nor
could the NHDF cells grow directly onto the gel due their lack of surface
properties. To
overcome this problem, the NHDF cells were grown on cell culture inserts
(Millice110,
Millipore Corp., Billerica, MA, USA) that was inserted into a well that
contained the test gel
diluted 1:1 against cell culture medium. The NHDF cells were cultivated in 24
well plates for
24 hours at 37C and 5% CO2 with Dulbecco's PBS cell culture media (FGM0-2 with
Insulin
(CC-4021J), rhFGF-B (CC-4065J) and FBS (CC-4161J), Lonza Walkervill, MD USA).
After
24 hours growing in presence of test substances or controls (no gel and
gelatin gel) 0.5 pL
3H-thymidine (Perkin Elmer, Boston, USA) was added into the wells containing
the cells. After
12 hours of exposure to thymidine the cells were washed three times in cold
PBS and lysed
with 250pL 1M NaOH. Then 200pL of the solubilized cell solution was
transferred to 3m1
Insta-gel-2-Pluss liquid scintillation fluid. Subsequently the scintillations
were counted in a
liquid scintillation analyser (TRI-Corb0 1500 Perkin Elmer).
Results and conclusion: There were no observed difference in count number
between
samples exposed to pluronic-Peroxide solution and the controls indicating that
the NHDF
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cells grew at normal rate in presence of these test gels. The hydrogen
peroxide containing
pluronic acid gels are safe and biocompatible. The SilvaSorb gel showed a
significant
decrease in count number indication slower cell growth in presence of this gel
as has also
been repeatedly reported in the scientific literature, indicating that this
gel is slightly toxic
NHDF cells.
Example 3
Chemical cleaning efficacy of liquid Pluronic f-127 solutions containing
peroxide
The following cleaning solutions were tested:
Negative control Brain Heart Infusion Broth (BHI broth)
Test 1 H202 3% v/v + f-127 1% w/v
Test 2 H202 5% v/v + f-127 1% w/v
Test 3 H202 3% v/v + f-127 7% w/v
Test 4 H202 5% v/v + f-127 7% w/v
Test 5 Chlorhexidine 0.2% w/v + f-127 7% w/v
Test 6 Ethanol 75% v/v + f-127 1% w/v
Experimental set-up:
A stock Streptococcus Epidermidis culture was established in BHI broth and
allowed to grow
to log phase.
The S. Epidermidis culture was introduced to cell culture disks of c.p.
titanium and allowed to
for a multilayer biofilm on the surface over a period of 2 days. After the
biofilm had been
established, the discs were rinsed several times in sterile, cold PBS until
only adherent cells
was present on the surfaces.
The discs with biofilm on were then submerged in test gel or control for 5
minutes 5 sec.
making sure that the entire discs were covered by the test gels all the time.
The discs were
then rinsed for 10 minutes in cold PBS on a shaker, rinsed off and viewed in a
table-top
scanning electron microscope to see how many bacteria that were left on the
test surfaces.
Results and conclusion:
This experiment showed that cleaning efficacy increased some with increasing
H202 and
increasing Pluronic f-127 concentration. The difference between test 1 and
test 4 was
however surprisingly small and not statistically significant, as all four
tests performed very
well and almost no bacteria remained on the surface. The negative control was
as expected
completely covered by bacteria with no effect of the PBS washing. The positive
Chlorhexidine and Ethanol controls was surprisingly ineffective. Almost all of
the biofilm was
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retained on the surfaces in these two groups. Later analysis with regrowth of
bacteria from
these surfaces revealed that all bacteria in these two tests were dead, but
that the bulk of
the biofilm remained attached to the surface, forming a contaminated layer
that provide a
strong bridgehead for new biofilm formation if a new contamination occurs.
The surprising finding in this study is that it seems to be a synergistic
effect between
hydrogen peroxide and Pluronic f-127 that not only kills bacteria but also
disintegrate and
solubilize the entire biofilm, leaving an almost totally decontaminated
surface (Figure3). The
concentration of the peroxide and pluronic can be reduced toward 3% hydrogen
peroxide in
1% pluronic acid without losing much effect compared to stronger solutions.
This also
indicates that the synergy between hydrogen peroxide and pluronic acid can be
fine-tuned
and probably has an optimal concentration-relation that allows for rapid and
dynamic micelle
(detergent and denaturation) effect and at the same time maintains the
effectiveness of
activated oxygen release that kills microbes and dissolves organic molecules.
This optimal
formulation appears to be lower in concentration of both peroxide and pluronic
when the
components are mixed together than what one would expect based on the effect
of the
separate components.
As is shown in Figure 3, titanium surfaces contaminated with S. Epidermidis
bacteria was
cleaned with growth medium (BHI, Negative control), H202 5% v/v + f-127 1% w/v
(Test 2),
H202 5% v/v + f-127 7% w/v (Test 4), Chlorhexidine 0,2% w/v + f-127 7% w/v
(Test 5) or
Ethanol 75% v/v + f-127 1% w/v. The negative control did not remove the
bacteria, nor was
the bacteria destroyed. The peroxide + pluronic acid mix killed all bacteria,
dissolved the
biofilm and removed the debris almost completely (Tests 2 & 4). Test 4 was
slightly, but not
statistically significant, more effective than Test 2. Chlorhexidine (Test 5)
and Ethanol (Test
6) did kill most of the bacteria but did not remove any debris from the
surface, leaving the
surfaces heavily contaminated. Surfaces visualized after cleaning in a
scanning electron
microscope. Scale bar is 20 micrometres.
Example 4
Staining of living and dead bacteria on decontaminated surfaces
Titanium surfaces contaminated with S. Epidermidis bacteria and grown to
biofilm in BHI
broth was removed from growth medium and submerged in sanitizing solution for
5 minutes
on a slow shaker. Discs were sanitized with A) saline (Negative control), B)
Chlorhexidine
0.2% w/v, or C) H202 3% v/v + f-127 pluronic Acid 5% w/v. After cleaning the
surfaces were
stained with fluorescent dyes, green for living microbes and red for dead
microbes. The
negative control (saline) did not remove any of the microbes, nor was the
biofilm removed.
The chlorhexidine killed all microbes but left the dead cells to contaminate
the surface. The
hydrogen peroxide + pluronic acid mix killed all microbes, dissolved the
biofilm and removed
the contamination almost completely. Surfaces were visualized in a confocal
microscope
after cleaning and staining (Figure 4).
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Example 5
Regrowth of S. Epidermidis after sanitizing a contaminated titanium surface
Regrowth of S. Epidermidis bacteria harbouring the luciferase gene making them
fluorescent, on sanitized titanium surfaces. Surfaces was first contaminated
with bacteria
and incubated in BHI broth until the surfaces were completely covered in
biofilm. The
titanium discs were then submerged in sanitizing solution and left on a slow
shaker for 5
minutes. After sanitizing the discs were rinsed in a large volume of sterile
water, then
covered by BHI medium again and incubated at 37 centigrade. At hourly
intervals the discs
were placed in a fluorometer to measure regrowth of bacteria by amount of
fluorescent as
compared to an untreated calibrated control and a sterile disc. The results
show (see figure
5B) that D) water with detergent (SDS 0,1% w/v), E) water with 5% pluronic
acid and F)
saline had minimal sanitizing effect, as regrowth of the biofilm occurred
within 3-4 hours after
cleaning. Chlorhexidine, 0,2%, on the other hand killed all bacteria with no
regrowth
observed although the dead biofilm stuck and remained on the surface (see
figure 3 and 4).
Hydrogen peroxide, 5% v/v, alone (A) cleaned the surface well as seen by a
delay of about
13 hours before the biofilm restored itself. However, hydrogen peroxide 3% v/v
combined
with 5% pluronic acid in water cleaned the surface significantly better,
delaying regrowth with
more than 15 hours (see also Figure 5A).
Example 6
Pluronic with peroxide is more skin-friendly than an alcohol containing hand-
sanitizer
Left and right thumbs were washed and sanitized four times daily for five
consecutive days
with a mix of A) pluronic acid (5% w/v) and hydrogen peroxide (3% v/v) or B)
Antibac
PharmaTM containing ethanol and propan-2-ol respectively. After completion of
the 5th day
sanitizing procedure both fingers were stained with a solution of Indian Red
(iron oxide) to
visualize fissures and cracks in the skin. After staining the fingers were
washed thoroughly in
warm water with soap, left to air dry and photographed in daylight. Fissures
and cracks in
the skin of the thumbs are easily visible as striated brown staining. The
Antibac PharmaTM
treated finger show deep fissures and cracks with callous, dry and hard skin.
The pluronic-
peroxide formulation however, caused no harm to the skin of the left thumb,
leaving skin
intact and tender. This demonstrate that the pluronic-peroxide formulation is
more
biocompatible and tissue friendly than alcohol-based hand sanitizers (Figure
6).
Example 7
Efficiency of sanitizing solutions on removing organic contaminants
To demonstrate the ability of hand sanitizers and cleaning solutions to remove
stains and
contamination from skin, a panel of products and solutions were tested against
stains of
permanent ink. Fingers were marked with a line of permanent blue ink (LyrecoTM
permanent
marker for laboratory use). The ink was applied with a pen and left to air-dry
for approx. 5
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minutes. The fingers were then cleaned with the various sanitizing solutions
for about 6-8
seconds, mimicking the normal application time for hand sanitizers in daily
life. The
sanitizing agent was thoroughly wiped off with paper tissue and the fingers
were
photographed with an iPhone X in daylight using the automatic exposure
control. The
5 intensity of the remaining stain is regarded to be an inverse visual gauge
for the cleaning
efficacy of the tested solutions. Finger A) was washed only with water. Finger
B) was
cleaned with warm water and soap. Finger C) was cleaned with 0.2%
chlorhexidine and
finger D) was rinsed with PyrispetTM (0.1% cetyl-pyridinium chloride). Finger
E) was cleaned
with Antibac PharmaTM (Alcohol based sanitizer containing ethanol and propan-2-
ol), finger
10 F) was cleaned with bleach (4% Sodium hypochlorite). Finger G) and H) was
rinsed with
hydrogen peroxide (1% and 5% v/v in water respectively). Finger I) was washed
in a solution
of pluronic acid f-127 in water (5% w/v). Finger J) was sanitized with a mix
of pluronic acid
(5% w/v) and hydrogen peroxide (1% v/v). The results show that bleach and
hydrogen
peroxide is very effective in removing the permanent ink stain. However,
surprisingly, the
15 most efficient removal of the stain is obtained by the combination of
pluronic acid and weak
hydrogen peroxide (Figure 7).
Example 8
Application for skin sanitizing, two-chamber dispenser bottle.
20 The two-component pluronic-Peroxide solution described here is intended for
hand sanitizing
after possible exposure to virus contamination. Virus are genetic code (RNA or
DNA)
wrapped in a protein envelope to protect and transmit the genetic information.
Most
sanitizers only attack (denature or fix) the protein envelope so that the
virus is no longer very
contagious, but do not remove the virus per se or attack the virus genome. The
combination
25 of peroxide and pluronic do both. The peroxide degrades both proteins and
RNA and DNA,
and the pluronic also denatures proteins and dissolves the organic material
into its micelle
structure, completely destroying and removing the viral particles from the
skin, together with
other contaminants and dirt.
30 A 500 ml dispenser bottle is divided in two chambers; one containing 400
milliliters of f-127
pluronic acid at 10% w/v in water, and one chamber containing 100 milliliters
of Hydrogen
Peroxide 25% v/v in water. A pump with two inlets pumps liquid from both
chambers into the
dispenser tip for mixing and application. The mixed solution is evenly
distributed over the
hands as with any other sanitizer, left to work for some seconds and is then
rinsed off under
running tap water. There is no need to apply any soap as the liquid itself
also work as a
detergent. The clean hands are dried off with a paper towel or air dried. No
extraordinary
precautions or actions are necessary to remove the solution. The solution is
completely
harmless after rinsing and will decompose to water, oxygen and carbon dioxide
with no
environmental footprint or impact.
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Example 9
Application for skin sanitizing, dispenser bottle with emulsion.
The two-component pluronic-peroxide solution described here is intended for
hand sanitizing
after possible exposure to virus contamination. Virus are genetic code (RNA or
DNA)
wrapped in a protein envelope to protect and transmit the genetic information.
Most
sanitizers only attack (denature or fix) the protein envelope so that the
virus is no longer very
contagious, but do not remove the virus per se or attack the virus genome. The
combination
of peroxide and pluronic do both. The peroxide degrades both proteins and RNA
and DNA,
and the pluronic also denatures proteins and dissolves the organic material
into its micelle
structure, completely destroying and removing the viral particles from the
skin, together with
other contaminants and dirt.
A 500 ml dispenser bottle contains a biphasic emulsion in two equal parts. One
part of the
emulsion contains f-127 pluronic acid in an oily suspension (10% w/v). Etheric
oils or
perfume can be added for pleasant smell. The other phase contains a water
solution with
hydrogen peroxide (10% v/v). Before application, the bottle is shaken
vigorously and a pump
with dispenser tip is used to apply the emulsion mix onto hands. The emulsion
is evenly
distributed over the hands as with any other sanitizer, left to work for some
seconds and is
then rinsed off under running tap water or simply left to air dry. There is no
need to apply any
soap as the liquid itself also work as a detergent. No extraordinary
precautions or actions is
necessary to remove the solution. The solution completely harmless after
rinsing and will
decompose to water, oxygen and carbon dioxide with no environmental footprint.
The
remaining oils will protect the skin from drying and make it smooth.
Example 10
Application for skin sanitizing, blister-in blister pack
The two-component pluronic-peroxide solution described here is intended for
hand sanitizing
after possible exposure to virus contamination. Virus are genetic code (RNA or
DNA)
wrapped in a protein envelope to protect and transmit the genetic information.
Most
sanitizers only attack (denature or fix) the protein envelope so that the
virus is no longer very
contagious, but do not remove the virus per se or attack the virus genome. The
combination
of peroxide and pluronic do both. The peroxide degrades both proteins and RNA
and DNA,
and the pluronic also denatures proteins and dissolves the organic material
into its micelle
structure, completely destroying and removing the viral particles from the
skin, together with
other contaminants and dirt.
A 1 ml blister pack is contained inside another 5 ml blister pack. The inner
blister pack
contains hydrogen peroxide (25 % v/v), the outer blister pack contains 3 ml f-
127 pluronic
acid in perfumed water (10 % w/v) and the first blister pack. When needed the
inner blister
pack is ruptured by applying manual force, then mixed by squeezing the outer
pack. After
mixing the outer blister pack is opened and the content is evenly distributed
over the hands
as with any other sanitizer, left to work for some seconds and is then rinsed
off under
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running tap water. There is no need to apply any soap as the liquid itself
also work as a
detergent. The clean hands are dried off with a paper towel or air dried. No
extraordinary
precautions or actions is necessary to remove the solution. The solution
completely
harmless after rinsing and will decompose to water, oxygen and carbon dioxide
with no
environmental footprint or impact.
Example 11
Application for skin sanitizing, wet wipes
The two-component pluronic-Peroxide solution described here is intended for
hand sanitizing
after possible exposure to virus contamination. Virus are genetic code (RNA or
DNA)
wrapped in a protein envelope to protect and transmit the genetic information.
Most
sanitizers only attack (denature or fix) the protein envelope so that the
virus is no longer very
contagious, but do not remove the virus per se or attack the virus genome. The
combination
of peroxide and pluronic do both. The peroxide degrades both proteins and RNA
and DNA,
and the pluronic also denatures proteins and dissolves the organic material
into its micelle
structure, completely destroying and removing the viral particles from the
skin, together with
other contaminants and dirt.
A 1 ml blister pack is contained inside another 5 ml blister pack. The inner
blister pack
contains hydrogen peroxide (25 % v/v), the outer blister pack contains 3 ml f-
127 pluronic
acid (10 % w/v) in perfumed water, a folded paper tissue and the first blister
pack. When
needed the inner blister pack is ruptured by applying manual force, then mixed
by squeezing
the pack. After mixing, the outer blister pack is opened and the folded paper
tissue, now
activated with the peroxide-pluronic mix used to wipe the skin, hands or
contaminated
surfaces free of dirt, microbes and viral contaminants. There is no need to
apply any soap as
the liquid itself also work as a detergent. The clean hands, skin or surface
is left to dry in air.
No extraordinary precautions or actions is necessary to remove the solution.
The solution
completely harmless after rinsing and will decompose to water, oxygen and
carbon dioxide
with no environmental footprint or harm to the skin.
Example 12
Mouth rinse application for oral sanitizing, dispenser bottle with emulsion
The two-component pluronic-peroxide solution described here is intended for
oral sanitizing
for microbial control or during a contagious viral pandemic. Virus are genetic
code (RNA or
DNA) wrapped in a protein envelope to protect and transmit the genetic
information. Most
viral sanitizers only attack (denature or fix) the protein envelope so that
the virus is no longer
very contagious, but do not remove the virus per se or attack the virus
genome. The
combination of peroxide and pluronic does both. The peroxide degrades both
proteins and
RNA and DNA, and the pluronic also denatures proteins and dissolves the
organic material
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33
into its micelle structure, completely destroying and removing the viral
particles from the oral
cavity and throat, together with other microbes, contaminants and mucus.
A 1000 ml dispenser bottle is divided in two chambers; one containing 800
milliliters of f-127
pluronic acid at 5% w/v in saline with sodium fluoride and taste and smell
modifiers, and one
chamber containing 200 milliliters of hydrogen peroxide 16% v/v in water. A
pump with two
inlets is used to pumps liquid from both chambers into the dispenser tip for
mixing and
application. 10 milliliters of the mixed solution are used to rinse the mouth
and throat for
about 1 minute, and then spat out in the sink. There is no need to brush teeth
or rinse with
water after application as the liquid itself is harmless to humans, but it is
no harm in doing it
either. No extraordinary precautions or actions is necessary to remove the
solution. The
solution completely harmless after rinsing and will decompose to water, oxygen
and carbon
dioxide with no environmental footprint or health impact.
The mouthwash can also be used against oral infections periodontitis and peri-
implantitis
and tooth decay, both prophylactically and for post-surgery infection control
and
maintenance treatment after periodontal or implant-related procedures. It can
also be used
to clean toothbrushes and intra-oral devices (dentures, anti-snoring devices,
orthodontic
appliances etc.) to avoid re-infection from repeated use.
Example 13
Nasal/sinus rinse
Nasal and sinus rinse applications, disposable bottles with applicator
The two-component pluronic-peroxide solution described here is intended for
nasal/sinus
rinsing against a rhinoviral infection causing congestion or for virus removal
during a
contagious flu or corona virus pandemic. Virus are genetic code (RNA or DNA)
wrapped in a
protein envelope to protect and transmit the genetic information. Most viral
sanitizers only
attack (denature or fix) the protein envelope so that the virus is no longer
very contagious,
but do not remove the virus per se or attack the virus genome. The combination
of peroxide
and pluronic does both. The peroxide degrades both proteins and RNA and DNA,
and the
pluronic also denatures proteins and dissolves the organic material into its
micelle structure,
completely destroying and removing the viral particles from the nasal cavity
and sinuses,
together with other contaminants and mucus.
Fifty milliliters of hydrogen peroxide (5% v/v in saline) is added to a 250 ml
disposable, soft
(squeezable) bottle with nasal applicator top containing 200 milliliters of f-
127 pluronic acid
at 1,25% w/v in saline and mixed by vigorous shaking. The head is placed over
a sink, and
the bottle containing the mix is then placed against one nostril and squeezed
carefully until
the fluid comes out of the other nostril and goes into the sink below. The
procedure is
repeated until the bottle is empty. Blow the nose after application is
completed. There is no
need to rinse with after application, the liquid itself is harmless to humans.
No extraordinary
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PCT/EP2021/057024
34
precautions or actions is necessary to remove the solution. The solution
completely
harmless after rinsing and will decompose to water, oxygen and carbon dioxide
with no
environmental footprint or health impact.
The nasal/sinus rinse can also be used against nasal infections or against
acute and chronic
sinusitis. The solution can also be used both prophylactically and for post-
surgery infection
control after otorhinolaryngeal procedures.
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