Note: Descriptions are shown in the official language in which they were submitted.
DISINFECTION METHOD COMPRISING A DISINFECTANT FORMED BY REACTION
OF H202 AND NO2 IN SITU WITH RETARDED RELEASE OF ACTIVE SUBSTANCE
[0001] Background of the invention
[0002] The present invention relates to a method and a device for the
disinfection of
surfaces, in particular for the disinfection of body parts, in particular of
hands, and/or in
particular for the disinfection of wounds.
[0003] The biocidal effect of the reaction products of hydrogen peroxide (H202
) and nitrite
(NO2-) with the addition of an acid is already known in literature.
[0004] For example, by mixing two initial solutions, one of which is H202 and
one of which
is NO2-containing, a disinfecting effect can be achieved, provided that the
inequation
t2
W = f k = [H202] = [N Oildt Wmin (1)
is satisfied. In this, W is the so-called efficacy parameter, which must be
greater than Wmin
to obtain an effect. The value Wmin may depend on the microorganism to be
inactivated,
respectively. Furthermore, k is the reaction rate of the reaction
H202 + NO Reaction products, (2)
which amongst others leads to the formation of short-lived reactive species,
particularly
peroxinitrite acid. Furthermore, (1) takes into account that during surface
decontamination
a distribution step has to be performed. This begins after the liquids have
been mixed at
time to and ends at time ti>to . Here, ti denotes the time at which the
surface to be
disinfected is completely wetted. The exposure time itself therefore only
starts at time ti
and ends at time t2.
[0005] Known methods for surface decontamination have the disadvantage that
the
reaction rate
R= k = [H2021= [N (3)
which according to equation (1) is responsible for the biocidal effect, is
highest directly
after mixing the two initial solutions, since according to equation (2) the
concentration of
the educts is also highest then. The reaction rate is strictly monotonically
decreasing for t
> to. Since the exposure time does not begin until ti > to, as a consequence,
a part of the
educts has already reacted with each other before the actual disinfection
process and is
no longer available during the exposure time. To nevertheless ensure a
sufficient effect
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Date Recue/Date Received 2021-11-10
during the exposure time, the initial reactant concentrations at time to must
be selected to
be significantly higher. This is disadvantageous, since high reactant
concentrations result
in increased costs for disinfectant supply and also present an increased risk
for the
disinfection application during the distribution period due to unintended
biocidal effects
with harmful consequences.
[0006] Therefore, the method described subsequently is aimed at the
decontamination of
surfaces by means of mixtures of NO2- and H202, wherein the reaction (1) is
retarded by
adding a suitable solvent, so that a considerably better effect can be
achieved compared
to the prior art. The retardation is achieved here by the retarding solvent
reducing the
reaction rate of the reaction (2), wherein the retarding effect decreases as
soon as the
concentration of the retarding solvent in the mixture is reduced, for example
by
evaporation of the solvent. In addition, the method according to the invention
permits
substantially longer processing times compared with known methods.
[0007] For the simultaneous discharge of fluids, for example, twin syringes
are known in
which two pistons are arranged in two cylinders and are mechanically connected
to each
other outside the cylinders at a common pressure element, so that when a
compressive
force is applied to the pressure element, the two pistons can be displaced
simultaneously
and can discharge fluids from the cylinders. However, this design also
requires pistons of
a respective length, which protrude from the cylinders before the fluids are
discharged and
require a corresponding amount of installation space.
[0008] This aspect is provided by a device suitable for carrying out the
method according
to the invention.
Description of the invention
Definitions
[0009] According to the present invention, the active solution comprises a
disinfecting
solution applied to the surface to be disinfected. Here, the surface refers to
a flat surface
or a surface with irregularities and/or cavities. The active solution may
contain, in addition
to the disinfecting agents formed in situ, additives. Such additives comprise,
but are not
limited to, solvents, buffer solutions, bases, fragrances, rust inhibitors,
complexing agents,
dyes and/or other disinfectants and/or ozone, as well as other reaction
products and
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Date Recue/Date Received 2021-11-10
reactive intermediates of the reaction between H202 and NO2-. According to the
present
invention, a dilution step comprises diluting the educts with solvents and/or
additives. The
dilution step precedes the mixing step or takes place simultaneously with the
mixing step.
[0010] According to the present invention, a mixing step comprises mixing
educts to obtain
the active solution. During the mixing step, additives may additionally be
mixed with the
educts. The mixing step may be composed of several sub-steps. The mixing step
starts
at time to = 0.
[0011] According to the present invention, a distribution step comprises
distributing the
active solution on the surface to be disinfected. Here, each point on the
surface to be
disinfected is wetted with active solution. The distribution step may start at
the same time
as the mixing step at time to or may follow it.
[0012] According to the present invention, the processing period ZA comprises
the mixing
step and the distribution step, i.e., the time required to mix the educts to
obtain the active
solution and to wet each point to be disinfected on the surface to be
disinfected with active
solution. The processing period begins at time to = 0 , when the educts are
first brought
into contact with each other, and ends at time ti , when each point on the
surface to be
disinfected is wetted with active solution. The pH value and temperature may
change
within the processing period particularly if the mixing takes place before the
first contact
with the surface and the surface affects the pH value and/or temperature. For
this reason,
the pH value and temperature are time-dependent during the process.
[0013] In the context of the invention, steps relevant to the disinfection
method, such as a
dilution step, can also take place before the processing period, i.e. before
time to = 0.
[0014] According to the present invention, an exposure step comprises exposure
of the
active solution to the surface wetted with active solution for disinfection.
The exposure
step is described by the exposure time ZE.
[0015] According to the present invention, the exposure time ZE comprises the
time period
required for the active solution to achieve a sufficient disinfection effect.
The exposure
time begins at time ti, at which every point of the surface to be disinfected
is wetted with
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Date Recue/Date Received 2021-11-10
active solution, and ends at time t2, at which every point of the surface
wetted with active
solution has been disinfected.
[0016] According to the present invention, NO2- is a nitrite salt having the
general formula
M,NO2 , wherein M is an alkali metal or an alkaline earth metal and x = 1 or x
= 2. In
particular, M is sodium or potassium and x = 1. The nitrite salt may be
present as a salt in
solution or as a solid. In this case, NO2 is in solution depending on the pH
value as anion
NO2- or as acid HNO2.
[0017] According to the present invention, the active ingredients, which are
the reaction
products of the reaction of H202 and NO2-, are formed in situ. In situ means
that the active
ingredients are generated only when needed.
[0018] According to the present invention, a stopping agent is a solvent which
comprises
a boiling temperature below 100 C and which slows down the reaction rate of
the reaction
between H202 and NO2-.
Description
[0019] A first aspect of the invention relates to a disinfection method for
surfaces
comprising providing an active solution comprising educts H202 and NO2-. The
method is
characterized in that the active solution comprises at least one stopping
agent, wherein
the stopping agent is a solvent having a boiling temperature below 100 C.
[0020] After mixing the educts H202 and NO2- to form an active solution, they
form short-
lived, reactive species, particularly peroxinitrite acid, which are
responsible for the biocidal
effect of the active solution. As described above, the reaction rate is
highest directly after
mixing, so that during the mixing process and subsequent distribution of the
active solution
on a surface to be disinfected, part of the educts already react with each
other and are
thus no longer available during the exposure period. The stopping agent
reduces the
reaction rate of the reaction between H202 and NO2-. The retarding effect
diminishes as
soon as the concentration of the retarding solvent in the mixture is reduced,
for example,
by evaporation of the solvent. Thus, the method according to the invention
allows longer
processing times.
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Date Recue/Date Received 2021-11-10
[0021] In some embodiments, the stopping agent is selected from an alcohol, a
ketone,
and an ester.
[0022] In some embodiments, the stopping agent is selected from methanol,
ethanol,
isopropanol, acetone, ethyl acetate, and n-propanol.
[0023] In some embodiments, the stopping agent is selected from ethanol,
isopropanol,
and acetone.
[0024] In some embodiments, the active solution is obtained by mixing the
educts H202
and NO2- and the stopping agent at time to.
[0025] Before mixing the educts, they can be present separately or partially
mixed. For
example, an H202 solution, an NO2- solution and the solvent (stopping agent)
can be
present separately. Alternatively, the stopping agent may be present in either
the H202
solution or the NO2- solution. It is also possible that a part of the stopping
agent is present
in the H202 solution and another part of the stopping agent is present in the
NO2- solution.
[0026] In some embodiments, the active solution is distributed on a surface to
be
disinfected until complete wetting at time ti.
[0027] In some embodiments, the time period between to and ti is at least 5
seconds.
[0028] In some embodiments, the time period between to and ti is at least 10
seconds.
[0029] In some embodiments, the time period between to and ti is at least 15
seconds.
[0030] Particularly in a medical context, hygiene regulations stipulate a
prescribed
distribution time for the active solution. Typically, active solutions for
hand disinfection are
distributed for at least 30 seconds.
[0031] In some embodiments, the active solution acts until time t2 to obtain a
disinfected
surface.
Date Recue/Date Received 2021-11-10
[0032] In some embodiments, the minimum concentration of stopping agent in the
active
solution at time to is at least 2.5% (v/v) and/or the maximum concentration of
stopping
agent in the active solution is < 90% (v/v), particularly < 60% (v/v), further
particularly <
40% (v/v).
[0033] In some embodiments, the minimum concentration of stopping agent in the
active
solution at time to is at least 2.5% (v/v).
[0034] Time to is the time of mixing, when the educts first come into contact
with each
other.
[0035] In some embodiments, the maximum concentration of stopping agent in the
active
solution is < 90% (v/v).
[0036] In some embodiments, the maximum concentration of stopping agent in the
active
solution is < 60% (v/v).
[0037] In some embodiments, the maximum concentration of stopping agent in the
active
solution is <40% (v/v).
[0038] After the distribution time, the reaction time starts at time ti. In
order to obtain at
least 20 % more educts in the active solution with stopping agent compared to
an active
solution without stopping agent, the condition from equation (100) must be
fulfilled.
crin (x)
crm(0) > 1,2 (100),
i
wherein
ctrniin(x) = min([1-1202] (x, t=ti), [NO](x, t=t1)),wherein x is the
concentration of the
stopping agent in volume percent with respect to the volume of the active
solution
at time t = to,
[H202] (x, t) describes the concentration of H202 at time t,
[NO2] (x, t) describes the concentration NO2- at time t.
crl'in(0) refers to an active solution without stopping agent.
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Date Recue/Date Received 2021-11-10
ctrniin corresponds to the maximum achievable efficacy W = f c k = [H202] =
[N OA dt,
wherein k denotes the rate constant of the reaction between H202 and NO2-,
i.e. the educt
whose concentration is lowest determines how much biocidal action is still
maximally
possible.
[0039] In some embodiments, the pH value of the active solution at time to is
between 1.
and 7.
[0040] In some embodiments, the pH value of the active solution at time to is
between 2
and 6.
[0041] In some embodiments, the pH value of the active solution at time to is
between 3
and 5.
[0042] In the event that the pH value cannot be readily determined, the
following definition
of the pH value applies in the context of the present invention: The pH value
of a solution
with x> 0 (i.e. with a solvent concentration (stopping agent) > 0%) is to be
defined as the
pH value measured with a pH electrode when the volume fraction of the solvent
(x) has
been replaced by water.
[0043] In some embodiments, the initial concentration [H202]0 at time to is
between 1 mM
and 1000 mM.
[0044] In some embodiments, the initial concentration [H202]0 at time to is
between 10 mM
and 500 mM.
[0045] In some embodiments, the initial concentration [H202]0 at time to is
between 15 mM
and 300 mM.
[0046] In some embodiments, the initial concentration [NO2]0 at time to is
between 1 mM
and 1000 mM.
[0047] In some embodiments, the initial concentration [NO2]0 at time to is
between 10 mM
and 500 mM.
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Date Recue/Date Received 2021-11-10
[0048] In some embodiments, the initial concentration [NO2]0 at time to is
between 15 mM
and 300 mM.
[0049] The disinfection process of the present invention comprising at least
the educts
H202 and NO2- consists of several substeps comprising at least:
= a mixing step wherein the educts are mixed to obtain an active solution;
= a distribution step in which the active solution is distributed on a
surface to be
disinfected,
wherein the mixing step and the distribution step take place in a processing
period le,
starting at time to when the educts are first brought into contact with each
other and ending
at time ti, when each point on the surface to be disinfected is wetted with
active solution,
wherein to is equal to 0 and ti is larger than to, and
= subsequently an exposure step in which the distributed active solution
acts on the
surface contacted with active solution over an exposure period ZE, which
begins at
time ti and ends after the time period ZE at time t2,
wherein t2 denotes the time at which each point on the surface contacted with
active
solution is wetted with active solution for a sufficient time to obtain a
disinfecting effect,
and wherein t2 is greater than ti,
the time-integrated reaction rate W over the exposure period ZE is represented
by the
integral
t2
W = fti k1 = [H202] = [N01] dt 10 mM, (5)
= wherein ti and t2 are as defined above, and
= wherein [H202] and [NO2] denote the concentrations of the educts during
the
exposure period ZE, and
= wherein k1 denotes the pH-dependent rate constant of the reaction between
H202
and NO2- or HNO2, and wherein the pH-value and the temperature may comprise
a time dependence, and in some embodiments, the maximum NO2 concentration
at time to of the mixing step is 300 mM.
[0050] In some embodiments, t2 does not exceed 3 minutes.
[0051] In some embodiments, the pH value of the active solution prior to
contact with the
surface to be disinfected is in the range of 2.1 pH <6.8.
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Date Recue/Date Received 2021-11-10
[0052] The pH-dependent rate constant k1 can be calculated as follows:
=
[H30]2 (6)
k4
(
KsH3o2 + [H30+1)(Kssivo2 + [H301)
,
with
k4 = 3,56 = 1014 exp (¨v,) (7)
Ks,Fm.r02 = 5,13 x 10 ¨4 (8)
Ks,H3q = 2 x 10 ¨2 (9)
and the unitless quantity
[H30] = 10¨PH (10)
with the effective activation energy EA = 70 kJ/mol and the temperature T. At
20 C, Ica is
120 M-15-1.
[0053] The time-dependent concentrations of the educts NO2- and H202 can be
calculated during the exposure time using the following equations:
[N01] = ¨A
' (11)
ki
[H20-)]
= A+D (12)
with
A=¨ _____________________________________________________________ (13)
1-exp(p(t-o)
[NO2 ,o',1
C = ____________________________________________________________ (14)
and
D = [H202]0 = (k1+ ¨ [N0110 = (15)
with k1, k4, Ksim02, KSHQ und [H301 as described above.
[H202/0 and [NO2] denote the initial concentrations at the time of the mixing
step of H202
and NO2- in the active solution. These are given by the educt concentrations
and the type
of mixing or dilution. For example, in the case of an educt concentration of
200 mM H202
in educt solution 1 and 200 mM NO2- in educt solution 2 and a mixing ratio of
1:1, initial
concentrations of [H202]0= [NO2]0= 100 mM are obtained.
[0054] In addition
r = 0,11, (16)
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Date Recue/Date Received 2021-11-10
wherein r is an outgassing coefficient describing the formation of NO, from
NO2- and is
described in more detail below.
[0055] As the starting substances (NO2- and H202) are converted over time, the
effective
reaction rate of the reaction between H202 and NO2- steadily decreases. Due to
the short
half-life of the reaction products, they are not accumulated and thus the
instantaneous
reaction rate of H202 and NO2- is decisive for the effectiveness of the active
solution at a
given time during the exposure period. For the use of the active solution as a
disinfectant,
it is necessary that the efficacy is given for a defined minimum duration of
action.
Therefore, the time-integrated reaction rate W must not fall below a minimum
value. The
heuristic equation (5) allows applicable concentrations of H202 and NO2- and a
respective
pH value to be selected for decontamination applications at a given process
temperature.
[0056] In contrast to vegetative bacteria, bacterial spores and non-enveloped
viruses
cannot be inactivated with alcohol-based agents or only after an
insufficiently long time.
At a reaction rate W 10 mM, not only vegetative bacteria but also bacterial
spores are
inactivated.
[0057] In an embodiment, the time-integrated reaction rate W of the reaction
between
H202 and NO2- is greater than or equal to 17.
[0058] At a reaction rate W 17 mM, not only vegetative bacteria and bacterial
spores but
also non-enveloped viruses are inactivated.
[0059] In an embodiment directed exclusively to vegetative bacteria, W = 0.3,
particularly
0.5.
[0060] A higher time-integrated reaction rate W increases the disinfecting
effect on the
surface contacted with active solution.
[0061] The processing period ZA comprises the mixing step and the distribution
step,
wherein the distribution step may start at the same time as the mixing step at
time to = 0,
or may follow it. The processing period starts at to = 0.
Date Recue/Date Received 2021-11-10
[0062] Furthermore, relevant steps can also take place before the processing
period, i.e.
before the time to = 0, such as a dilution step. However, these steps are not
relevant for
the time interval for calculating the time-integrated reaction rate and can
therefore be
before to = 0.
[0063] The processing period must be sufficiently long to wet every point of
the surface to
be disinfected with active solution. At the same time, however, the processing
time should
not be too long so that after distribution of the active solution on the
surface to be
disinfected, sufficient reactive active solution is still present to achieve a
disinfecting effect
and the necessary portion of stopping agent is relatively low at the same
time.
[0064] In some embodiments, the processing period ending at time ti is
selected from a
range of 0 < ti 5 75 s, in particular is selected from the range 0 <t1 5 30 s,
in particular is
selected from a range 0 < ti 15 s, in particular is selected from a range 0 <
ti 2 s.
[0065] In some embodiments, the exposure time begins after 2 s.
[0066] In some embodiments, the exposure time begins after 15 s.
[0067] In some embodiments, the exposure time begins after 30 s.
[0068] In some embodiments, the exposure time begins after 75 s.
[0069] In some embodiments, a longer processing period is required, ending at
time ti,
wherein this is selected from a range of 15 < ti 75 s, particularly selected
from a range
of 30 <t1 75 s, particularly selected from a range of 50 <t1 75 s.
[0070] In some embodiments, a shorter processing period is required, ending at
time ti,
wherein this is selected from a range of 0 < ti 30 s, in particular selected
from the range
0 < ti 15 s, in particular selected from a range 0 < ti 2 s.
[0071] In some embodiments, a processing period ending at time ti is required,
wherein
this is selected from a region of 2 < ti 75 s, in particular selected from the
region
2 < ti 30 s, in particular selected from a region 2 < ti 15 s.
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Date Recue/Date Received 2021-11-10
[0072] Furthermore, the time range (the sum of ZA and ZE), particularly for
applications in
hand disinfection, should be sufficiently short to achieve the necessary
disinfecting effect
in a region that is still appropriate. An excessively long time period, such
as more than 10
minutes, is neither practicable nor sensible to use for hand disinfection,
even in the clinical
region.
[0073] The mixing of educts H202 and NO2- to produce the active solution can
take place
before contact with the surface to be disinfected, or take place directly on
the surface to
be disinfected. The mixing step can take place without external influence by
diffusion and
convection, be supported by mechanical distribution, or be integrated in a
spraying
process in which the educts are sprayed together onto the surface to be
disinfected.
[0074] Furthermore, the pH value plays a decisive role in the disinfection
process
according to the invention.
[0075] In some embodiments, the pH value of the active solution on the surface
contacted
with active solution is located in the range of 2.1 pH
6.8, particularly in a range of
2.5 pH 5, and particularly in a range of 3.3 pH 4.7.
[0076] The reaction rate of the reaction between H202 and NO2- depends on the
pH value
of the solution according to (6). With decreasing pH values, i.e. with
increasing
concentration of H30+ , the reaction rate k1 increases. At low pH values,
therefore, the
disinfecting effect of the active solution is higher, but low pH values do not
allow a
sufficiently long processing and exposure period due to the high reaction rate
of H202 and
NO2- in combination with the short-lived nature of the reaction products
formed. At higher
pH values, the reaction rate of H202 and NO2- decreases significantly, which,
however,
also reduces the disinfecting effect of the active solution.
[0077] In contrast to decontamination in suspensions, it was found that
acidification can
lead to a significant deterioration of the effect when decontaminating
surfaces. This results
from the need for the liquid to be applied and/or distributed on the surface
in a distribution
step and, in the case of structured and porous surfaces, to penetrate the
surface by
diffusion. The active solution must not lose its disinfecting effect during
this time, however,
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Date Recue/Date Received 2021-11-10
this is caused by a pH value that is too low. In this case, the educts are
degraded too
quickly before they can exert their antimicrobial effect at any point on the
surface. This
problem is solved by the present invention for an active solution of at least
NO2- and H202
by identifying a range of pH values in which use as a surface disinfection
agent is possible.
[0078] Many surfaces themselves have a pH-regulating property, in particular a
buffering
effect, such as the skin surface. The pH value which is decisive for the
method of the
present invention is therefore the pH value which results on the surface
wetted with active
solution. Such buffering surfaces and their buffering effect are known to the
skilled person.
[0079] In an embodiment of the present invention, the disinfection method is
to be used
for disinfection of a surface strongly buffering the pH value, in particular
skin, wounds or
other organic surfaces, wherein a suitable pH value on the surface results
from the fact
that the pH value of the active solution prior to contact with the surface to
be disinfected
is in the range of 2.1 to 4.5, in particular in a range of 2.1 to 3.6, in
particular in a range of
2.1 to 3.2.
[0080] This pH value is increased by 0.2 to 1.7, in particular by 0.2 to 0.8,
by contact with
the buffering surface, depending on the surface properties.
[0081] As a result, the pH value of the active solution is lower than the pH
value of the
active solution on the surface to be disinfected. Due to this property, the
educts react
quickly outside the surface to be disinfected and do not accumulate in the
environment.
On the surface to be disinfected, however, particularly on the surface of a
body part,
particularly a hand, the reaction between H202 and NO2- due to the buffering
effect of the
surface proceeds somewhat more slowly, allowing the disinfecting effect to
unfold. Thus,
the disinfecting effect remains effective for a sufficiently long time on the
intended surface;
on surfaces not intended for this purpose, rapid degradation of the educts
takes place and
thus no accumulation occurs.
[0082] In an embodiment, the initial quantities of the educts are identical,
particularly in
applications where outgassing of NO, is negligible, thus NO2- and H202 are
completely
converted. Thus, no biocidal active substances are released into the
environment.
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Date Recue/Date Received 2021-11-10
[0083] In an embodiment, the efficiency E = W/Wmõ of the method at process-
dependent
predetermined times ti and t2 is at least 10%, particularly at least 20%,
particularly at least
30%, wherein
14/max = min( [H202]0, [NOi]o ) (exp(¨Gti) ¨ exp(¨Gt2)) (17)
with G = in (L) 1 (t 2 ¨ t1) denoting the ti maximum achievable efficacy
parameter and
minaH202]0, [NO2]0) denoting the minimum concentration selected from the
initial
concentrations [H202]0 and [NO2]0. This ensures that the educts used are
efficient by
reasonable selection of the selectable process parameters pH value,
temperature and
initial concentrations of the educts.
[0084] In an embodiment, the initial quantities of educts differ from each
other by less than
%, in particular the initial quantity of NO2- is 2 % to 10 % higher than the
initial quantity
of H202. The exact value is to be determined for a given application, i.e. for
a given surface
and amount of liquid. In this case, only nitrate and water are formed as
stable end
products, while NO2- and H202 are completely converted. As a result, no
biocidal active
substances are released into the environment. The disinfection method
according to the
invention is thus particularly environmentally friendly.
[0085] A slightly higher initial amount of NO2- compared to H202 is helpful to
prevent the
loss of effective NO2- due to outgassing of NO,.
[0086] The outgassing of NO, is significantly greater for surface disinfection
due to the
larger surface area than for disinfection that takes place in solution or
suspension. When
the active solution is distributed over a surface, only a thin film of liquid
is formed, during
which large portions of the NO2 used can be released as gaseous nitrogen
oxides (NO,).
One of the consequences of this is that up to 10 % of the NO2- introduced into
the liquid is
outgassed in the form of NO(g) or particularly NO2(g). The outgassing leads to
an
accelerated degradation of NO2- in an active solution of H202 and NO2- on
surfaces,
compared to an identically prepared active solution in suspension. The
outgassing
influences the reaction kinetics and should also be kept low for health
reasons.
[0087] The NO, emissions are to be attributed to two basic processes: On the
one hand,
the use of an acid to adjust the pH value can directly cause NO, outgassing,
for example
the process:
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Date Recue/Date Received 2021-11-10
HNO2 + HNO2 NO + NO2 + H20 NO(g) + NO2(g) + H20. (18)
shown in Fig. 1.
[0088] The presence of H202 is not required for process (18). On the other
hand, the
formation of ONOOH, which requires the presence of H202, can be achieved by
the
reaction (19)
ONOOH NO2 + OH (19)
by subsequent outgassing of NO2 contributing to NO, emissions.
[0089] The outgassing of NO has been studied in experiments and computer
simulations.
In an embodiment of the present invention, the outgassing is expressed as the
outgassing
rate by the equation
Rdegas = R1 x r, (20)
which can be assumed proportional to the effective annihilation rate R1 of NO2-
and H202
by reaction (1), and contributes to the annihilation of NO2- corresponding to
the equation
d[No]
¨dt = ¨R1¨ Rdegas = ¨1-c1[H202][N01] x (1 + r). (21)
Here, r denotes a portion related to R 1, which leads to the outgassing of NO2-
in the form
of NO,. This form results from the reaction
ONOOH NO2 + OH (22)
making the essential contribution to outgassing during surface
decontamination. While r
in suspension experiments is usually negligibly small, approximately in the
range of r
0.01, r in surface decontamination can adopt values in the range of r 0.11.
The specific
value depends on the application in question, in particular on the layer
thickness of the
liquid film. Thus, the outgassing that occurs influences the reaction kinetics
of the reaction
of H202 and NO2- in the case of surface disinfection, which would be
negligible in the case
of disinfection in suspension.
[0090] One possible way to delimit the amount of outgassing NOR, is to delimit
the initial
concentration of NO2-.
[0091] Thus, in some embodiments, a maximum initial concentration of NO2- at
time to
does not exceed a concentration of 300 mM, particularly 200 mM, particularly
100 mM.
Date Recue/Date Received 2021-11-10
[0092] The disinfection method according to the invention can be used for the
disinfection
of surfaces. The disinfection method according to the invention can be used in
particular
for disinfection of skin and/or for disinfection of wounds.
[0093] The disinfection method of the present invention may further be
employed for
decontaminating medical devices, particularly thermolabile medical devices
such as
endoscope tubing, as well as containers and tubs.
[0094] The disinfection method of the present invention may further be used to
decontaminate seeds, crops, animal products, food, packaging as well as
beverage
containers or beverage lines.
[0095] In an embodiment of the disinfection method according to the invention,
acid
buffers or acid buffer solutions can be added to the educts and/or the active
solution. For
example, citrate buffer, acetic acid-acetate buffer, phosphate-citrate buffer,
phosphate
buffer or citrate buffer can be used as buffers. Buffer solutions containing
citrate are
particularly suitable because of their pleasant odor.
[0096] In an embodiment of the disinfection method according to the invention,
additives
may be added to the educts before and/or during the mixing step. Conceivable
additives
comprise, among others, solvents, bases, fragrances, dyes and/or further
disinfectants,
and/or ozone.
[0097] Furthermore, suspensions with non-water-soluble substances can be
produced, in
particular by admixing fats and surfactants.
[0098] In a further embodiment, one or more plasma sources may be used to
produce
one or more of the educts.
[0099] Thus, it would be possible to produce the educts H202 and NO2- from air
and water
using electricity. The state of the art discloses plasma methods sufficiently
for the skilled
person to select a respective plasma.
16
Date Recue/Date Received 2021-11-10
[0100] In a further embodiment of the present invention, the plasma
additionally produces
ozone, which may be part of the active solution.
[0101] The disinfection method for surfaces, which is the subject of this
invention, is
characterized in that it has a sporicidal effect. There is no approved
disinfectant in
Germany for the disinfection of skin that also has a disinfecting effect
against bacterial
spores. Furthermore, the method according to the invention has a low odor and
is
advantageous compared to conventional disinfection methods for the
disinfection of skin,
because it does not dry out the skin.
[0102] Another aspect of the invention provides a device for simultaneous
delivery of at
least two volume flows of H202 and NO2- solutions, in particular of at least
two volume
flows of the same size, comprising at least two reservoirs for receiving H202
and for
receiving NO2-, and, arranged in a respective reservoir, a displaceable piston
for
conveying a fluid from the respective reservoir, wherein the pistons are
coupled to one
another via a force-transmitting apparatus in such a way that they can be
displaced
synchronously parallel to one another, so that the fluids can be discharged
from the
reservoirs at the same time, in particular with the same volume flows.
[0103] The stopping agent can either be included in one or both of the H202
and NO2
volume flows or added via a third volume flow.
[0104] The pistons can be displaced simultaneously at the same speed. This
means that
the pistons also have the same acceleration behavior, so that completely
identical
movement sequences on two movement paths arranged parallel to each other can
be
realized with them, so that the fluids can be discharged simultaneously with a
fixed mixing
ratio.
[0105] In particular, the two reservoirs may be arranged in a common
cartridge.
[0106] In an embodiment, the device for simultaneous delivery of at least two
volume flows
of H202 and NO2- is characterized in that the two reservoirs are separated
from each other
by at least one common partition wall, wherein this partition wall comprises a
lower
bending strength than the sides of the pistons sliding on the partition wall
and wherein a
17
Date Recue/Date Received 2021-11-10
first piston comprises a projection projecting in the direction of a second
piston and the
second piston comprises a recess which is essentially complementary with
respect to the
shape and size of the projection, so that when one piston is displaced, the
respective other
piston is entrained in the recess whilst deforming the partition wall via
indirect mechanical
engagement of the projection.
[0107] Mechanical engagement takes place only indirectly, since a region of
the
sectionally deformed partition wall, designed in particular as a diaphragm,
continues to be
arranged between the projection and the recess.
[0108] In an embodiment, the device for simultaneous delivery of at least two
volume flows
of H202 and NO2- is characterized in that the reservoirs are separated from
one another
by at least one common partition wall, wherein the pistons are connected via
at least one
connecting member which is arranged to cut the partition wall located
therebetween at
least sectionwise upon displacement of the pistons.
[0109] For this purpose, the connecting member is preferably equipped with a
wedge
segment or a cutting edge or blade with which it is possible to cut into or
slice the partition
wall, which is designed in particular as a diaphragm, even when little force
is applied to
the pistons.
[0110] In an embodiment, the connecting member with the cutting edge is
located on the
side of the pistons opposite the respective outlets from the reservoirs with
respect to the
axis of movement of the piston unit realized by means of the connecting
member.
[0111] In an embodiment, the device for simultaneous delivery of at least two
volume flows
of H202 and NO2- is characterized in that each reservoir comprises an outlet,
wherein a
fluid conduit is connected to a respective outlet, which is fluidically
connected to a mixing
unit for mixing the fluids from the reservoirs.
[0112] Such a mixing unit can be, for example, a so-called T-piece, in which
the fluids
from two reservoirs are combined.
18
Date Recue/Date Received 2021-11-10
[0113] In a further advantageous embodiment of the device according to the
invention, it
is provided that a check valve is arranged in the flow path between a
respective outlet and
the mixing unit, respectively, for preventing mixed fluid from flowing back
into the
reservoirs.
[0114] In an embodiment, the device for simultaneous delivery of at least two
volumetric
flows of H202 and NO2- is characterized in that a first pump is fluidically
connected to the
mixing unit for generating a negative pressure and thus for conveying the
mixture of fluids
from the mixing unit.
[0115] In an embodiment, the device for simultaneous delivery of at least two
volume flows
of H202 and NO2- is characterized in that the device comprises an outlet
device, in
particular a nozzle, with which the fluids can be discharged as a mixture in
liquid form or
also as a spray mist.
[0116] In an embodiment, the device for simultaneous delivery of at least two
volume flows
of H202 and NO2- is characterized in that the force transmission apparatus
comprises one
force transmission element for each piston, with which a force can be applied
to one piston
respectively for the purpose of displacing the piston, wherein the two force
transmission
elements are mechanically coupled to one another.
[0117] In particular, this mechanical coupling can be implemented on or by
means of a
thrust apparatus, with which a force can be exerted respectively on a
respective force
transmission element, which in turn transmits this force to the respective
piston.
[0118] In an embodiment, the device for simultaneous delivery of at least two
volumetric
flows of H202 and NO2- is characterized in that the force transmission
apparatus is
assigned to at least one piston and comprises, fluidically coupled to the
latter, in particular
delimited by the latter at least in certain regions on one side, a pressure
chamber to which
a second pump for generating an overpressure is fluidically connected, so that
the
respective piston is displaced when the second pump is actuated and an
overpressure is
generated.
19
Date Recue/Date Received 2021-11-10
[0119] This means that on its side opposite the fluid to be discharged, the
piston is
fluidically connected to the second pump for generating an overpressure, so
that when the
overpressure is generated on the side of the piston facing away, from the
fluid, this piston
is displaced and conveys the fluid out of the reservoir assigned to it
accordingly.
[0120] Several pistons can be assigned to a common pressure chamber.
[0121] In an embodiment, the device for simultaneous delivery of at least two
volume flows
of H202 and NO2- is characterized in that the device comprises three
reservoirs, wherein
a displaceable third piston is arranged in the third reservoir for delivery of
a fluid from the
third reservoir, wherein the three pistons are coupled to each other via a
force transmission
apparatus such that they are synchronously displaceable parallel to each
other, so that
the fluids can be delivered from the reservoirs with equal volume flows.
[0122] In an embodiment, the device for simultaneously delivering at least two
volume
flows of H202 and NO2- is characterized in that at least a first reservoir is
neighbouring on
at least two sides of at least a further reservoir, wherein in the further
reservoir the fluid
comprises a lower translucency than the fluid in the first reservoir for the
purpose of
reducing light irradiation into the fluid in the first reservoir.
[0123] In a specific embodiment, it is provided that the first reservoir is
completely
surrounded by two further reservoirs.
[0124] In a further aspect of the invention, a method is provided for
simultaneously
delivering at least two volume flows of H202 and NO2- , in particular at least
two volume
flows of the same size, wherein at least two reservoirs comprising H202 and
NO2- are
provided, and in a respective reservoir a piston is displaced for delivering a
respective
fluid from the respective reservoir, wherein the pistons are coupled to one
another via a
force transmission apparatus in such a way that they are displaced
synchronously parallel
to one another, so that the fluids are discharged from the reservoirs at the
same time, in
particular with equal volume flows.
Date Recue/Date Received 2021-11-10
[0125] In embodiments with only two reservoirs, the stopping agent is in one
or both of
the volume flows of H202 and NO2-. In the presence of a third reservoir, the
stopping agent
can be added alternatively or additionally via this reservoir.
[0126] Reference listing:
1 Device
2 Cartridge
3 Opening
Volume flow to the first reservoir
11 Volume flow to the second reservoir
First reservoir
21 Second reservoir
22 Third reservoir
23 Outer reservoir
24 Inner reservoir
Partition wall
26 Bending zone
First piston
31 Second piston
32 Third piston
33 Projection
34 Recess
Thrust of the pistons
36 Force transmission elements
50 Connecting member
51 Blade
60 First pump
61 Check valves
62 Mixing unit
63 Nozzle
64 Pressure chamber
65 Second pump
21
Date Recue/Date Received 2021-11-10
Brief description of the figures
[0127]
Figure 1 shows the concentration curve (top) and the reaction rate according
to
equation (3) (bottom) with [H2021, = [NO2]0 = 20 mM as well as a pH value of
3.3 and
a temperature of 37 C. The filled region illustrates the integral over the
reaction time
from ti = 15s to t2 = 75s.
Figure 2 shows the influence of isopropanol concentration IPA on the reaction
coefficient of reaction (2) at 20 C.
Figure 3 shows the isopropanol concentration of an initially 50 % isopropanol
solution
after 0 s, 30 s and 60 s on a metal plate heated to 37 C. The isopropanol
concentration of the isopropanol solution is shown in Figure 3.
Figure 4 shows the assumed concentration curve of isopropanol (top), the
calculated
concentration curve of H202 and NO2- (middle) and the reaction rate (bottom)
respective to equation (3) with rate constant (9) and initial concentrations
[H202 lc) =
[NO2]0 = 20 mM as well as a pH value of 3.2 and a temperature of 37 C. The
filled
region illustrates the integral over the exposure time from ti = 15 s to t2 =
75 s.
Figure 5 shows the concentration curve of nitrite when 10 % ethanol, acetone
or
isopropanol is added.
Figure 6 shows the inactivation of spores of Bacillus atrophaeus in the
experiment
without preceding mixing of the educts (direct) as well as with preceding
mixing of the
educts (premixed) (see section "Microbiological examinations ").
Figure 7 shows the time course of the concentrations [H202] and [NO2-] at
initial
concentrations [H202]2, = [NO2]0 = 50 mM, a pH value of 3.2 at 20 C (top) as
well as
the ratio ntrniin(x)intmlin(0) (bottom). The dashed line indicates the ratio
ntmlin(x)/ntmlin(0) = 1,2.
Fig. 8 shows a device according to the invention in perspective view;
22
Date Recue/Date Received 2021-11-10
Fig. 9 shows a sectional view of the device shown in Fig. 1;
Fig. 10 shows a part of the sectional view in Fig. 2;
Fig. 11 shows a part of the sectional view from Fig. 2 during a cutting
process;
Fig. 12 shows the cutting process in another side view;
Fig. 13 shows the two pistons with the connecting member in top view;
Fig. 14 shows a part of the device according to the invention with mixing unit
and first
pump;
Fig. 15 shows the device according to the invention with two force
transmission
elements;
Fig. 16 shows the device according to the invention with the pressure chamber;
Fig. 17 shows three pistons connected to one another during the cutting
process;
Fig. 18 shows three reservoirs with triangular cross-section; and
Fig. 19 shows three reservoirs with a central arrangement of a reservoir.
Detailed description of figures 8 to 19
[0128] A cartridge 2 as part of the device 1 according to the invention is
shown in Figures
8 and 9 as an example with two reservoirs 20, 21. Figure 8 shows a cartridge 2
which has
two reservoirs 20, 21 which are separated from each other by a partition wall
25 in the
form of a membrane. The device 1 has two openings 3 into which the respective
fluids can
be introduced. The pistons 30,31 are displaceable in the reservoirs 20,21
along a direction
of movement, wherein they can only be moved in the thrust direction, i.e.
tangentially to
the partition wall 25. The movement of the pistons 30,31 takes place to reduce
the volume
of a respective reservoir 20,21 so that fluid received in a respective
reservoir 20,21 is
expelled.
23
Date Recue/Date Received 2021-11-10
[0129] The movement of the two pistons 30,31 cannot occur independently of
each other
in this case. The device 1 is designed in such a way that the pistons 31,31
can only move
synchronously so that they always generate a respective volume flow 10,11 of
fluid to the
same extent. In particular, both reservoirs 20,21 can comprise the same size
and both
pistons 30,31 can comprise the same cross-section, so that the two volume
flows 10,11
are also equal.
[0130] Figure 10 shows the pistons 30, 31 and a partition wall 25 formed as a
membrane
of the device 30, 31 according to the invention, in which the pistons 30, 31
are indirectly
mechanically coupled in that a first piston 30 has a projection 33 and a
second,
neighbouring piston 31 has a recess 34 of complementary shape and size, so
that the
projection 33 engages indirectly in the recess 34 and in this way, when one
piston 30, 31
moves, the other piston 30, 31 is carried along. The partition wall 25, formed
as a
membrane, is here designed to be so little bend-resistant or flexible that it
can form a
respective bending zone 26 in the region of the engagement of the projection
33 in the
recess 34.
[0131] Figures 11, 12 and 13 show pistons 30, 31 and partition 25 of an
embodiment of
the device 1 in which the pistons 30, 31 are mechanically coupled by means of
a
connecting member 50 so that they can only be displaced together. The
connecting
member 50 is designed as a blade 51. In particular, the pistons 30, 31 and the
connecting
member 50 can be made of the same material, so that a single, coherent piston
unit
results.
[0132] Figure 14 shows how the fluid can be extracted by a first pump 60,
which exerts a
suction on the fluids in the reservoirs 20,21. Here, uncontrolled mixing of
the two fluids in
the reservoirs 20,21 is prevented by two check valves 61. The mixing of the
two fluids
takes place downstream of the valves 61, in the so-called dead volume, which
is realized
by a mixing unit 62, located upstream of the first pump 60. In contrast to the
extraction of
the fluids with two individual pumps, this design has the advantage that in
the event of a
malfunction of the first pump 60, no fluid can be discharged, so that the
malfunction is
directly apparent to the user.
24
Date Recue/Date Received 2021-11-10
[0133] The mixture of fluids may be dispensed, nebulized, or sprayed from the
nozzle 63
for further use as a liquid.
[0134] Figure 15 shows an implementation of the device 1 in which the thrust
of the
pistons 30, 31 is realized mechanically, wherein a force transmission element
36 is
connected to a respective piston so that both pistons 30, 31 can be displaced
synchronously by introducing forces through the force transmission elements
36.
[0135] Figure 16 shows an implementation of the device 1 in which the thrust
of the pistons
35 is realized by the effect of a gas pressure on the pistons 30, 31. In this
case, a common
pressure chamber 64 is assigned to the two pistons 30, 31 shown, as well as a
second
pump 65, which is set up to generate an overpressure in the pressure chamber
64, so that
the two pistons 30, 31 can be displaced simultaneously or synchronously due to
the
overpressure.
[0136] Figure 17 shows an implementation of the device 1 with three pistons
30, 31, 32
during the cutting process, wherein the coupling of the pistons is implemented
here
exemplarily in that the pistons 30, 31, 32 are designed as one continuous
piston. A
partition 25 is arranged between two of the three pistons 30,31,32,
respectively.
[0137] Figure 18 shows a first reservoir 20, a second reservoir 21 and a third
reservoir 22,
and that the partition walls 25 do not necessarily need to be arranged
parallel to each
other. In particular, at least one reservoir 20,21,22 may fully or partially
enclose at least
one other reservoir, as shown in Figure 18. This is advantageous in order to
protect the
fluid in the inner reservoir, particularly a fluid containing H202, from light
irradiation and
consequent decomposition of H202, for example by adding a respective dye to
the fluid in
an outer reservoir, thereby reducing the translucency of the fluid in the
outer reservoir and
consequently the light irradiation on the fluid in the inner reservoir.
[0138] Figure 19 shows an exemplary arrangement of three reservoirs 20,21,22
of the
device 1, wherein the two outer reservoirs 23 surround the inner reservoir 24,
also to
reduce or avoid light irradiation into the liquid in the inner reservoir 24.
Date Recue/Date Received 2021-11-10
Examples
Disinfection process without retarding solvent
[0139] The pH-dependent rate constant k = ko can be calculated as follows:
[H3012
k0 = k* (40)
(KsH302 + + [H30+1)(Ks,HNO2 + [H30+])
,
with
k* = 3,56 = 1014 exp(¨v) M-1-s-1- (50)
Ks,HNO2 = 5,13 x 10-4 (60)
Ks,
H3 0+2 = 2 x 10 ¨2
(70)
and the unitless quantity
[H30] = 10-PH (80)
with an effective activation energy EA = 70 kJ/mol and the temperature T.
[0140] As an example, by solving the differential equations resulting from (2)
for the
concentrations [H202] and [NO2] at the same starting concentrations at time to
of
[H202]0 = [NO2]0 = 20 mM as well as a pH value of 3.2 and a temperature of 37
C, the
concentration curves shown in Figure 1 above are obtained. In Figure 1 below,
the
reaction rate is given according to equation (3). The filled region in Figure
1 below
illustrates the integral (1) with to = 15 s and ti = 75 s, wherein in this
case an efficacy
parameter of W(15 s to 75 s) = 3.8 mM is obtained. As can be easily seen from
Figure 1
below, the agent is more effective during the distribution step than during
the actual
exposure time: calculating the integral (1) during the processing time, i.e.
with to= Os and
ti = 15 s, gives an efficacy parameter of W(0 s to 15 s) = 14.7 mM. Thus, a
large part of
the effective potential is not utilized. The duration of the distribution step
depends on the
respective process and cannot be freely selected or arbitrarily shortened. For
example, a
distribution time of 30 s is common for hygienic hand disinfection.
26
Date Recue/Date Received 2021-11-10
Experiments performed
Influence of isopropanol on the rate constant
[0141] Figure 2 shows the influence of isopropanol (IPA) added to the active
solutions on
the rate constant (40) at a temperature of 20 C. The measurement of the
reaction
constant was carried out here using UV spectroscopy, wherein the decrease in
NO2-
concentration was quantified to determine the reaction rate. As shown in
Figure 2, the
reaction (2) can be effectively slowed down by adding isopropanol. The
influence of the
isopropanol concentration on the reaction rate of reaction (2) can be taken
into account
by multiplying the rate constant ko by a factor dependent on the isopropanol
concentration
IPA (given in volume percent) according to
k = /co x exp(-0,129 x IPA) (90)
Temporal change of isopropanol concentration on surfaces
[0142] If a solution of water and a solvent with a higher vapor pressure than
water is
applied to a surface, the solvent evaporates more quickly, reducing its
proportion in the
solution. The following experiment was performed for this purpose: A metal
plate with an
area of 567 cm2 was heated to a temperature of (37 2) C. 3 mL of an
isopropanol
solution was spread on the plate. After waiting for 30 s or 60 s, the liquid
remaining on the
surface was collected in a vessel and the density of the liquid was
determined. For this
purpose, the weight of 100 pL of the collected liquid was measured. From the
data
presented in Chu, Kwang-Yu, and A. Ralph Thompson. Journal of chemical and
engineering data 7.3 (1962): 358-360 regarding the concentration dependence of
the
density of isopropanol solutions, the isopropanol concentration of the
collected liquid was
determined. Furthermore, for verification of the method, the density of the
isopropanol
solution was determined before it was applied to the metal plate (designated
"0 s" in Figure
3) as well as from distilled water (H20 dest ). The selected temperature and
area are
particularly relevant as a model for hand disinfection. In this case, the
active solution is
also heated by body heat and frictional heat when hand disinfection is carried
out as
prescribed. In addition, an even greater surface-to-volume ratio of the
distributed active
solution occurs during hand disinfection due to the surface properties of the
skin.
27
Date Recue/Date Received 2021-11-10
Temporal change of the reaction rate (3) on surfaces
[0143] The concentration dependence (90) together with the time variation of
the
isopropanol concentration shown in Figure 3 can be exploited to retard the
progress of the
reaction (2). Figure 4 (top) shows the time course of an assumed isopropanol
concentration during surface disinfection with a solution of H202 and NO2-.
Figure 4
(middle) shows the concentrations of [H202] and [NO2] resulting from equations
(1) and
(90), wherein the initial concentrations are [H202]) = [NO2]0 =20 mM, pH value
3.2 and
temperature 37 C. Thus, with the exception of the isopropanol concentration,
the same
conditions were chosen as in the calculation shown in Figure 1. However, with
the reaction
time starting at ti = 15 s and ending at t2 = 75 s, the efficacy parameter
here is WHDA (15 s
to 45 s) = 13.1 mM due to the retarded reaction. This is 9.3 mM higher
compared to the
value of W(15 s to 45 s) = 3.8 mM obtained without the use of IPA. This
demonstrates that
adding a solvent that decreases the reaction rate of reaction (2) produces a
more effective
disinfectant.
[0144] Figure 5 shows the influence of different solvents on the reaction rate
of reaction
2. The measurements were carried out using UV spectroscopy with an absorption
length
of 1 cm and at a wavelength of 332 nm.
Microbiological examinations
[0145] In order to verify the retarded microbiological effect when using a
stopping solution,
the effect of the active solution on spores of the species Bacillus atrophaeus
was
investigated in two experiments.
[0146] In the first experiment, 10 pL of a spore solution (containing spores
of the bacterium
of species Bacillus atrophaeus ) was placed in a reaction vessel. Then, 495 pL
of a 50
mM NaNO2 solution was added, followed by 495 pL of a 50 mM H202 solution to
obtain
an active solution. Here, the NaNO2 solution and the H202 solution
respectively contained
the same concentration of isopropanol selected from 0 %, 5 %, 10 %, 15 % or 20
%,
wherein the percentages refer to percent by volume. In addition, the H202
solution was
acidified using 25 mM H3PO4. The reaction was stopped after an incubation time
of 60 s
by dilution in a neutralization solution and then plated out on agar. After an
incubation
period of 24 h, the colony forming units were quantified on the respective
agar plate.
28
Date Recue/Date Received 2021-11-10
[0147] The results of this test are shown in Figure 6 (measurement series
"direct"). The
specified "log10 reduction" is the negative decadic logarithm of the
determined
concentration of colony-forming units after application of the respective
active solution in
relation to the determined bacteria concentration in a negative control. As
can be seen
from the data, the addition of isopropanol leads to a deterioration in the
effect of the
respective active solution. In the light of the preceding investigations, it
is clear that the
deterioration of the effect is due to a reduction in the reaction rate, for
example, in
accordance with equation (90).
[0148] In the second experiment, 10 pL of a spore solution (B . atrophaseus )
was
introduced analogously to the first experiment. In a separate reaction vessel,
1 mL of a 75
mM NaNO2 solution was added and reacted with 1 mL of a 75 mM H202 solution to
obtain
an active solution. After 15s of reaction time, 990 pL of this active solution
was added to
the spore solution. Analogous to the first experiment, the NaNO2 solution and
the H202
solution respectively contained the same concentration of isopropanol selected
from 0 %,
%, 10 %, 15 % or 20 %. In addition, the H202 solution was acidified using 37.5
mM
H3PO4. The higher concentrations of the educts compared to the first
experiment were
chosen here to approximately compensate for the loss of these educts during
the 15 s
reaction time. Analogous to the first experiment, the solution was diluted in
neutralization
solution after 60 s of reaction time and plated out.
[0149] The results of this experiment are shown in Figure 6 ("premixed" series
of
measurements). As can be seen from this, the addition of isopropanol in this
experiment
leads to an improvement in the sporicidal effect for isopropanol
concentrations of up to 15
% ¨ the trend is thus contrary to the observation in the first experiment.
However, this is
also due to the fact that the isopropanol acts as a stopping solution here. As
a result, the
reaction proceeds more slowly during the 15 s reaction time, so that even more
educts
are available during the exposure time. At an isopropanol concentration of 20
%, the
reaction in this experiment is already slowed down to such an extent that
fewer educts
(compared with the 15 % experiment) are converted during the exposure time and
the
effect is therefore inferior.
29
Date Recue/Date Received 2021-11-10
Example of determining the minimum solvent concentration that can be used
Definitions
[0150]
= The total process time is the distribution time + drying time. The
distribution time
ends at time
= Drying time = time until wetted surface is completely dry, ends at time
t2.
= ctmlin(x) = min(cH202(x, t=ti), cNc(x, t=t1)), where x is the
concentration of the
stopping agent in volume percent relative to the volume of the active solution
at
time t=to.
The function min(a,b) is equal to a if a < b, b if b a.
ctmi in (0) refers to an active solution without stopping agent.
ctrniin corresponds to the maximum achievable efficacy W= k =
[H202] = [NOndt,
wherein k denotes the rate constant of the reaction between H202 and NO2-.
It is advantageous if the total process time is as short as possible. It is
also advantageous
if the efficacy is as high as possible during the drying time. The drying time
can always be
shortened by adding an alcohol with a lower boiling temperature than water.
[0151] In addition, the efficacy is increased by adding alcohol in the drying
time. The
following points must be taken into account when designing the alcohol
concentration:
a) Minimum alcohol addition:
The alcohol concentration must be chosen so that the condition
Ctmi in (X)
__________________________________ >12 (100),
c' (0)
is satisfied.
b) Maximum alcohol addition:
Too high an alcohol concentration can lead to unwanted changes in the treated
surfaces or, in the case of application to the skin, to skin irritation, so
the alcohol
concentration should be chosen as low as possible. In particular, the alcohol
concentration should be less than 90 %, in particular less than 60 %, in
particular
less than 40 %.
[0152] Figure 7 (top) shows an example of the concentration curve for NO2 and
H202 for
admixtures of 0, 2.5, 5.0, 7.5 and 10.0 % isopropanol. Figure 7 (bottom) shows
the ratios
Date Recue/Date Received 2021-11-10
ntrniin(x)intmlin(0). In addition, the dashed line indicates the required 20 %
improvement,
so that the region to be selected according to the invention can be read off
from equation
(X).
Determination of the minimum applicable solvent concentration
[0153] A disinfectant is required which permits a distribution time of at
least 15 s,
comprises a pH value of 3.2 and wherein isopropanol is used as the retarding
solvent. The
following steps are to be carried out:
1. The concentration of H202 and NO2- are to be measured time-resolved at a
given
pH value after mixing the components for different isopropanol concentrations.
This can be carried our, for example, using UV spectroscopy as indicated in
PCT/EP2019/062897 and above (see Figure 7 above).
2. For the selected isopropanol concentrations x, the ratio ntrniin (x)initVn
(0) is to be
determined (see Figure 7 below) and the condition ntrniin(x)intmlin(0) > 1,2
is to be
verified. In this example, an isopropanol concentration of 2.5 % is the
minimum
solvent concentration that can be used.
[0154] For other solvents and pH values, analogous steps must be taken.
Literature list:
[0155] Zhu, Ling, Christopher Gunn, and Joseph S. Beckman. "Bactericidal
activity of
peroxynitrite." Archives of biochemistry and biophysics 298.2 (1992): 452-457.
[0156] Chu, Kwang-Yu, and A. Ralph Thompson. "Densities and Refractive Indices
of
Alcohol-Water Solutions of n-Propyl, Isopropyl, and Methyl Alcohols." Journal
of chemical
and engineering data 7.3 (1962): 358-360.
31
Date Recue/Date Received 2021-11-10
