DISINFECTION METHOD COMPRISING A DISINFECTANT FORMED BY REACTION OF H.SUB.2.O.SUB.2 AND NO.SUB.2 IN SITU WITH RETARDED RELEASE OF THE ACTIVE SUBSTANCE

20230293751 · 2023-09-21

Assignee

Inventors

Cpc classification

International classification

Abstract

The invention relates to a method for disinfecting surfaces comprising providing an active solution comprising the reactants H.sub.2O.sub.2 and NO.sub.2.sup.-, wherein the active solution comprises at least one stopping agent, wherein the stopping agent is a solvent having a boiling temperature below 100° C. Furthermore, the invention relates to a device for the application of this process.

Claims

1. A disinfection method for surfaces, comprising providing an active solution comprising educts H.sub.2O.sub.2 and NO.sub.2.sup.-, characterized in that the active solution comprises at least one stopping agent for reducing the reaction rate of H.sub.2O.sub.2 and NO.sub.2.sup.-, wherein the stopping agent is a solvent having a boiling temperature below 100° C.

2. The method of claim 1, wherein the stopping agent is selected from an alcohol, a ketone and an ester, in particular methanol, ethanol, isopropanol, acetone, ethyl acetate and n-propanol, further in particular ethanol, isopropanol and acetone.

3. The method according to claim 1, wherein the active solution is obtained by mixing the educts H.sub.2O.sub.2 and NO.sub.2.sup.- and the stopping agent at time t.sub.0.

4. The method according to claim 1, wherein the active solution is distributed on a surface to be disinfected until complete wetting at time t.sub.1.

5. The method according to claim 1, wherein the time period between t.sub.0 and t.sub.1 is at least 5 seconds, in particular at least 10 seconds, further in particular at least 15 seconds.

6. The method according to claim 1, wherein the active solution acts until time t.sub.2 to obtain a disinfected surface.

7. The method according to claim 1, wherein the minimum concentration of the stopping agent in the active solution at time t.sub.0 is at least 2.5 % (v/v) and/or the maximum concentration of the stopping agent in the active solution is < 90% (v/v), in particular < 60% (v/v), further in particular < 40% (v/v).

8. The method according to claim 1, wherein the pH-value of the active solution at time t.sub.0 is between 1 and 7, in particular between 2 and 6, in particular between 3 and 5.

9. The method according to claim 1, wherein the initial concentration [H.sub.2O.sub.2].sub.0 at time t.sub.0 is between 1 mM and 1000 mM, in particularly between 10 mM and 500 mM, in particular between 15 and 300 mM.

10. The method according to claim 1, wherein the initial concentration [NO.sub.2.sup.-].sub.0 at time t.sub.0 is between 1 mM and 1000 mM, in particular between 10 mM and 500 mM, in particular between 15 and 300 mM.

11. Device 1 for the simultaneous delivery of at least two volume flows 10, 11 of H.sub.2O.sub.2 and NO.sub.2 solutions, in particular of at least two volume flows 10, 11 of the same size, comprising at least two reservoirs 20, 21 for receiving H.sub.2O.sub.2 and for receiving NO.sub.2, and, arranged in a respective reservoir 20, 21, a displaceable piston 30, 31 for conveying a fluid from the respective reservoir, the pistons 30, 31 being coupled to one another via a force transmission 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 20, 21 at the same time, in particular with same volume flows 10, 11.

12. Device 1 for simultaneous delivery of at least two volume flows 10, 11 of H.sub.2O.sub.2 and NO.sub.2.sup.- according to claim 11, characterized in that the two reservoirs 20, 21 are separated from each other by at least one common partition wall 25, wherein this partition wall 25 has a lower bending strength than the sides of the pistons 30, 31 sliding on the partition wall 25, and wherein a first piston 30 has a projection 33 projecting in the direction of a second piston 31 and the second piston 31 has a recess 34 which is essentially complementary with respect to the shape and size of the projection 33, so that when one piston is displaced, the respective other piston is entrained in the recess 34 whilst deforming the partition wall 25 via an indirect mechanical engagement of the projection 33.

13. Device 1 for simultaneous delivery of at least two volume flows 10, 11 of H.sub.2O.sub.2 and NO.sub.2.sup.- according to claim 12, characterized in that the reservoirs 20, 21 are separated from one another by at least one common partition wall 25, wherein the pistons 30, 31 are connected via at least one connecting member 50, which is configured to cut the partition wall 25 located therebetween at least sectionwise upon displacement of the pistons 30, 31.

14. Device 1 for simultaneous delivery of at least two volume flows of H.sub.2O.sub.2 and NO.sub.2.sup.- according to claim 11, characterized in that the device comprises three reservoirs 20, 21, 22, wherein in the third reservoir 22 a displaceable third piston 32 is arranged for conveying a fluid from the third reservoir 22, wherein the three pistons 30, 31, 32 are coupled to each other via a force transmission apparatus in such a way that they are synchronously displaceable parallel to one another, so that the fluids can be discharged from the reservoirs 20, 21, 22 with the same volume flows.

15. Device for simultaneous delivery of at least two volume flows of H.sub.2O.sub.2 and NO.sub.2.sup.- according to claim 11, characterized in that at least a first reservoir 20 is neighboring on at least two sides of at least a further reservoir 21, 22, wherein in the further reservoir 21, 21 the fluid comprises a lower translucency than the fluid in the first reservoir 20 for the purpose of reducing light irradiation into the fluid in the first reservoir 20.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0136] FIG. 1 shows the concentration curve (top) and the reaction rate according to equation (3) (bottom) with [H.sub.2O.sub.2].sub.0 = [NO.sub.2.sup.-]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 t.sub.1 = 15 s to t.sub.2 = 75 s.

[0137] FIG. 2 shows the influence of isopropanol concentration IPA on the reaction coefficient of reaction (2) at 20° C.

[0138] FIG. 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 FIG. 3.

[0139] FIG. 4 shows the assumed concentration curve of isopropanol (top), the calculated concentration curve of H.sub.2O.sub.2 and NO.sub.2.sup.- (middle) and the reaction rate (bottom) respective to equation (3) with rate constant (9) and initial concentrations [H.sub.2O.sub.2].sub.0 = [NO.sub.2.sup.-].sub.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 t.sub.1 = 15 s to t.sub.2 = 75 s.

[0140] FIG. 5 shows the concentration curve of nitrite when 10% ethanol, acetone or isopropanol is added.

[0141] FIG. 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”).

[0142] FIG. 7 shows the time course of the concentrations [H.sub.2O.sub.2] and [NO.sub.2.sup.-] at initial concentrations [H.sub.2O.sub.2].sub.0 = [NO.sub.2.sup.-].sub.0 = 50 mM, a pH value of 3.2 at 20° C. (top) as well as the ratio

[00030]nt1minx/nt1min0

(bottom). The dashed line indicates the ratio

[00031]nt1minx/nt1min0=1,2.

[0143] FIG. 8 shows a device according to the invention in perspective view,

[0144] FIG. 9 shows a sectional view of the device shown in FIG. 1,

[0145] FIG. 10 shows a part of the sectional view in FIG. 2,

[0146] FIG. 11 shows a part of the sectional view from FIG. 2 during a cutting process,

[0147] FIG. 12 shows the cutting process in another side view,

[0148] FIG. 13 shows the two pistons with the connecting member in top view,

[0149] FIG. 14 shows a part of the device according to the invention with mixing unit and first pump,

[0150] FIG. 15 shows the device according to the invention with two force transmission elements,

[0151] FIG. 16 shows the device according to the invention with the pressure chamber,

[0152] FIG. 17 shows three pistons connected to one another during the cutting process,

[0153] FIG. 18 shows three reservoirs with triangular cross-section, and

[0154] FIG. 19 shows three reservoirs with a central arrangement of a reservoir.

DETAILED DESCRIPTION OF FIGS. 8 TO 19

[0155] A cartridge 2 as part of the device 1 according to the invention is shown in FIGS. 8 and 9 as an example with two reservoirs 20, 21. FIG. 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.

[0156] 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.

[0157] FIG. 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.

[0158] FIGS. 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.

[0159] FIG. 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.

[0160] The mixture of fluids may be dispensed, nebulized, or sprayed from the nozzle 63 for further use as a liquid.

[0161] FIG. 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.

[0162] FIG. 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.

[0163] FIG. 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.

[0164] FIG. 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 FIG. 18. This is advantageous in order to protect the fluid in the inner reservoir, particularly a fluid containing H.sub.2O.sub.2, from light irradiation and consequent decomposition of H.sub.2O.sub.2, 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.

[0165] FIG. 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.

EXAMPLES

Disinfection Process Without Retarding Solvent

[0166] The pH-dependent rate constant k = k.sub.0 can be calculated as follows:

[00032]k0=k*H3O+2KS,H3O2++H3O+KS,HNO2+H3O+­­­(40)

with

[00033]k*=3,561014expEARTM1S1­­­(50)

[00034]KS,HNO2=5,13×104­­­(60)

[00035]KS,H3O2+=2×102­­­(70)

and the unitless quantity

[00036]H3O+=10pH­­­(80)

with an effective activation energy E.sub.A = 70 kJ/mol and the temperature T.

[0167] As an example, by solving the differential equations resulting from (2) for the concentrations [H.sub.2O.sub.2] and [NO.sub.2.sup.-] at the same starting concentrations at time t.sub.0 of [H.sub.2O.sub.2].sub.0 = [NO.sub.2.sup.-]0 = 20 mM as well as a pH value of 3.2 and a temperature of 37° C., the concentration curves shown in FIG. 1 above are obtained. In FIG. 1 below, the reaction rate is given according to equation (3). The filled region in FIG. 1 below illustrates the integral (1) with t.sub.0 = 15 s and t.sub.1 = 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 FIG. 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 t.sub.0 = 0 s and t.sub.1 = 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.

EXPERIMENTS PERFORMED

Influence of Isopropanol on the Rate Constant

[0168] FIG. 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 NO.sub.2.sup.- concentration was quantified to determine the reaction rate. As shown in FIG. 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 k.sub.0 by a factor dependent on the isopropanol concentration IPA (given in volume percent) according to

[00037]k=k0×exp0,129×IPA­­­(90)

Temporal Change of Isopropanol Concentration on Surfaces

[0169] 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 cm.sup.2 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 .Math.L 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 FIG. 3) as well as from distilled water (H.sub.2O 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.

Temporal Change of the Reaction Rate (3) on Surfaces

[0170] The concentration dependence (90) together with the time variation of the isopropanol concentration shown in FIG. 3 can be exploited to retard the progress of the reaction (2). FIG. 4 (top) shows the time course of an assumed isopropanol concentration during surface disinfection with a solution of H.sub.2O.sub.2 and NO.sub.2.sup.-. FIG. 4 (middle) shows the concentrations of [H.sub.2O.sub.2] and [NO.sub.2.sup.-] resulting from equations (1) and (90), wherein the initial concentrations are [H.sub.2O.sub.2].sub.0 = [NO.sub.2.sup.-]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 FIG. 1. However, with the reaction time starting at t.sub.1 = 15 s and ending at t.sub.2 = 75 s, the efficacy parameter here is W.sub.IPA (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.

[0171] FIG. 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

[0172] 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.

[0173] In the first experiment, 10 .Math.L of a spore solution (containing spores of the bacterium of species Bacillus atrophaeus ) was placed in a reaction vessel. Then, 495 .Math.L of a 50 mM NaNO.sub.2 solution was added, followed by 495 .Math.L of a 50 mM H.sub.2O.sub.2 solution to obtain an active solution. Here, the NaNO.sub.2 solution and the H.sub.2O.sub.2 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 H.sub.2O.sub.2 solution was acidified using 25 mM H.sub.3PO.sub.4. 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.

[0174] The results of this test are shown in FIG. 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).

[0175] In the second experiment, 10 .Math.L of a spore solution (B. atrophaseus ) was introduced analogously to the first experiment. In a separate reaction vessel, 1 mL of a 75 mM NaNO.sub.2 solution was added and reacted with 1 mL of a 75 mM H.sub.2O.sub.2 solution to obtain an active solution. After 15 s of reaction time, 990 .Math.L of this active solution was added to the spore solution. Analogous to the first experiment, the NaNO.sub.2 solution and the H.sub.2O.sub.2 solution respectively contained the same concentration of isopropanol selected from 0%, 5%, 10%, 15% or 20%. In addition, the H.sub.2O.sub.2 solution was acidified using 37.5 mM H.sub.3PO.sub.4. 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.

[0176] The results of this experiment are shown in FIG. 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.

EXAMPLE OF DETERMINING THE MINIMUM SOLVENT CONCENTRATION THAT CAN BE USED

Definitions

[0177] The total process time is the distribution time + drying time. The distribution time ends at time t.sub.1.

[0178] • Drying time = time until wetted surface is completely dry, ends at time t.sub.2.

[0179] •

[00038]ct1minx=minCH2O2x,t=t1,CNO2¯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=t.sub.0.

[0180] The function min(a,b) is equal to a if a < b, b if b ≤ a.

[00039]ct1min0

refers to an active solution without stopping agent.

[00040]ct1min

corresponds to the maximum achievable efficacy W=

[00041]W=t1kH2O2NO2dt,

wherein k denotes the rate constant of the reaction between H.sub.2O.sub.2 and NO.sub.2.sup.-. 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.

[0181] 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: [0182] a) Minimum alcohol addition: The alcohol concentration must be chosen so that the condition is satisfied. [0183] 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%.

[0184] FIG. 7 (top) shows an example of the concentration curve for NO.sub.2 and H.sub.2O.sub.2 for admixtures of 0, 2.5, 5.0, 7.5 and 10.0% isopropanol. FIG. 7 (bottom) shows the ratios

[00043]nt1minx/nt1min0.

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

[0185] 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: [0186] 1. The concentration of H.sub.2O.sub.2 and NO.sub.2.sup.- 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 FIG. 7 above). [0187] 2. For the selected isopropanol concentrations x, the ratio is to be determined (see FIG. 7 below) and the condition to be verified. In this example, an isopropanol concentration of 2.5% is the minimum solvent concentration that can be used.

[0188] For other solvents and pH values, analogous steps must be taken.

LITERATURE LIST

[0189] Zhu, Ling, Christopher Gunn, and Joseph S. Beckman. “Bactericidal activity of peroxynitrite.” Archives of biochemistry and biophysics 298.2 (1992): 452-457 . [0190] 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 .