Rinse solution for a photodynamic disinfection

EP4525996A1Pending Publication Date: 2025-03-26MANA HEALTH TECH GMBH
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Patent Information

Application Number
EP2023721835
Authority / Receiving Office
EP · EP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2022-05-16
Filing Date
2023-04-17
Publication Date
2025-03-26

AI Technical Summary

Technical Problem

Current photodynamic disinfection methods for mouth disinfection are not sufficiently effective in reducing biofilm and pathogens without being more complex or difficult to use.

Method used

A rinsing solution containing riboflavin 5'-phosphate sodium, another photosensitizer, glycerol, hyaluronic acid sodium salt, xylitol, L-arginine, and urea, which, when irradiated, produces reactive oxygen species to effectively destroy biofilm and pathogens, while being easy to use and requiring minimal radiation exposure.

Benefits of technology

The solution achieves a significant reduction in biofilm and pathogens, with the balanced interaction of ingredients enhancing the biocidal effect by several orders of magnitude, making it more effective than conventional mouthwashes without the need for prolonged or intense radiation.

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Abstract

The invention relates to a rinse solution for a photodynamic disinfection, in particular an oral disinfection, containing, in each case based on the total rinse solution, at least one photosensitizer from the group consisting of riboflavin 5'-phosphate sodium in a proportion of 0.2 to 0.6 wt% and another photosensitizer in the form of riboflavin 5'-phosphate sodium in a proportion of 0.001 to 0.05 wt.%, at least one viscosity modulator from the group of glycerol in a proportion of 1.0 to 5.0 wt.% and hyaluronic sodium salt in a proportion of 0.01 to 0.3 wt.%, at least one biofilm inhibitor from the group of xylitol in a proportion of 7.0 to 25.0 wt.%, L-arginine in a proportion of 0.1 to 0.5 wt.%, and urea in a proportion of 0.5 to 3.0 wt.%, and a remainder based on water.
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Description

[0001]Rinsing solution for photodynamic disinfection The present invention relates to a rinsing solution for photodynamic disinfection, in particular mouth disinfection. During photodynamic disinfection, harmful microorganisms, e.g. in the mouth or on a mucous membrane, in a wound or a natural or, for example, surgically created body opening, on the skin surface or an artificial surface, are destroyed through the interaction of light irradiation and a photosensitizer. During mouth disinfection, for example, a biofilm on the teeth and gums, usually formed by bacteria, is removed, thereby combating, for example, caries, gingivitis and periodontitis. When rinsing with the rinsing solution, the photosensitizer penetrates the microorganisms or attaches itself to them and is activated by the irradiation. This generates free radicals, e.g. reactive oxygen species (“ROS”).The free radicals are neither carcinogenic nor genotoxic to humans and act as a biocide, i.e., a substance that destroys pathogens, e.g., fungi (including their spores), bacteria, parasites, and viruses. Depending on the type of photosensitizer, it acts during photodynamic disinfection either as a catalyst that generates free radicals from the environment upon exposure, e.g., from a solution containing the photosensitizer; or the photosensitizer itself releases free radicals upon irradiation. The wavelength of the radiation emitted by the radiation source must be matched to the photosensitizer used and its absorption spectrum; it generally ranges from the ultraviolet to the infrared range. In recent years, many different photosensitizers have been investigated and used for photodynamic disinfection, e.g., of hands, mouth, teeth, wounds, etc.suggested; for example, US 2016 / 0051833 A1 mentions chlorophyllin sodium copper salt, riboflavin, allura red, indigo carmine, erioglaucine, tartrazine, chromotrope, fast green (“fast green”), lissamine green B, acridine, phenazine, cyanine, phenothiazine, porphyrin, phthalocynine, and other photodynamically active substances that can be added to toothpaste or mouthwash for oral disinfection. Furthermore, it is suggested to add other ingredients, e.g., caries-inhibiting, antibacterial, abrasive, anti-inflammatory, moisture-regulating substances, flavorings, dyes, etc. The biofilm reduction achieved with the proposed rinsing solutions orToothpastes containing these photosensitizers have a pH value of between 18% and 72% after irradiation for up to 15 minutes, and thus, depending on the photosensitizer, are even significantly lower or only slightly higher than with a conventional mouthwash without a photosensitizer and without complex irradiation. The aim of the invention is to create a rinsing solution for photodynamic disinfection, in particular oral disinfection, which is significantly more effective in reducing pathogens, in particular biofilm, without being more difficult or complex to use. This aim is achieved with a rinsing solution for photodynamic disinfection, in particular oral disinfection, which contains at least one photosensitizer from the group consisting of riboflavin 5'-phosphate sodium in a proportion of 0.2 to 0.6% by weight and a photosensitizer other than riboflavin 5'-phosphate sodium in a proportion of 0.001 to 0.05% by weight.-%, at least one viscosity modulator from the group glycerol in a proportion of 1.0 to 5.0 wt.% and hyaluronic acid sodium salt in a proportion of 0.01 to 0.3 wt.%, at least one biofilm inhibitor from the group xylitol in a proportion of 7.0 to 25.0 wt.%, L-arginine in a proportion of 0.01 to 0.5 wt.% and urea in a proportion of 0.5 to 3.0 wt.%, and the remainder water-based. The stated proportions are in each case based on the total rinsing solution. The present invention is based on the finding that not only the choice of photosensitizer or its concentration has a significant influence on the effectiveness of the rinsing solution during irradiation, but that it is precisely the balanced interaction of the various ingredients in the appropriate concentration that produces a surprising, unforeseeable increase in effectiveness, namely a reduction in bacteria by several orders of magnitude.Thus, at least one biofilm inhibitor in the specified concentration weakens the integrity of the biofilm by inhibiting the metabolism of the biofilm-forming bacteria, breaking their interlinking, and / or reducing the surface tension of the biofilm. The at least one viscosity modulator in the specified substance selection and concentration causes a thin, slightly adhesive film containing the biofilm inhibitor(s) and photosensitizer(s) to form on the bacterial structures to be reduced during rinsing for subsequent irradiation for photodynamic disinfection, thereby significantly enhancing the effect of the biofilm inhibitor(s) and photosensitizer(s) without the entire rinsing solution having to be retained, e.g., in the mouth or on the skin, during irradiation; i.e., the mouth or another part of the body can be easily and conveniently rinsed with the rinsing solution before irradiation.The at least one photosensitizer ultimately produces the particularly strong biocidal effect resulting from the formulation of the rinsing solution, i.e. without particularly long-lasting or intensive irradiation, i.e. conveniently, easily and without additional effort. As photosensitizer(s), in addition to or instead of the aforementioned riboflavin 5'-phosphate sodium, various substances with a photodynamic effect can be used, in particular water-soluble photosensitizers, e.g. phycocyanin, but also fat-soluble photosensitizers, if they are e.g. liposomally encapsulated or made soluble in the water base with the help of emulsifiers, nanoparticle carriers or the like. A single photosensitizer or two or more different photosensitizers can be used. The water base can, as is known to the person skilled in the art, be, for example, water, distilled water or flavored water.a mixture of water and hydrolate (particularly eucalyptus or peppermint hydrolate); alternatively, the water base is an aqueous system to which buffers known in the art are added to stabilize the pH. For example, to improve solubility, as protection against demixing, to preserve the rinsing solution, etc., other ingredients known in the art can be added to the water base, each acting, for example, as a buffer system, preservative, carrier system, solubilizer, surfactant or emulsifier and / or promoting micelle formation in the rinsing solution. It is advantageous if the at least one photosensitizer or one of the (several) photosensitizers mentioned is riboflavin 5'-phosphate sodium in a proportion of 0.25 to 0.45 wt.%, preferably in a proportion of 0.3 wt.%, of the rinsing solution.This photosensitizer has proven particularly effective in the rinsing solution, particularly in the concentration ranges mentioned. Riboflavin 5'-phosphate sodium is – in addition to its pronounced photodynamic effect – skin-care and, as an essential vitamin, promotes skin and mucous membrane health and, for example, tooth enamel strength. Alternatively or additionally, it is advantageous if the photosensitizer(s) is phycocyanin in the stated proportion of 0.001 to 0.05 wt.%, preferably in a proportion of 0.005 to 0.025 wt.%, of the rinsing solution. Furthermore, it is advantageous if the photosensitizer(s) is methylene blue in the stated proportion of 0.001 to 0.05 wt.%, preferably in a proportion of 0.005 to 0.025 wt.%, of the rinsing solution.These two photosensitizers, phycocyanin and methylene blue, have proven particularly useful and effective—either individually, together, or with another photosensitizer, particularly riboflavin 5'-phosphate sodium. A particularly suitable rinsing solution is obtained when the viscosity modulator(s) is glycerol in a proportion of 2.0 to 3.0 wt.%, preferably 2.5 wt.%, of the rinsing solution. Glycerol not only regulates viscosity, so that the biofilm is effectively and sustainably wetted in the specified concentration ranges, but also has a mucosal smoothing and moisturizing effect. This wetting is further favorably influenced if the or one of the viscose modulators is hyaluronic acid sodium salt in a proportion of 0.02 to 0.1 wt.%, preferably in a proportion of 0.025 wt.%, of the rinsing solution.In addition to its viscosity-regulating effect, hyaluronic acid sodium salt is also a humectant and has an anti-inflammatory effect in the concentration ranges mentioned. Preferably, the biofilm inhibitor(s) is xylitol in a proportion of 15.0 to 25.0 wt.%, preferably 15.0 wt.%, of the rinsing solution. Due to its bacteriostatic effect, xylitol is a particularly suitable biofilm inhibitor in the specified concentration. In a favorable variant of the rinsing solution, the biofilm inhibitor(s) is L-arginine in a proportion of 0.01 to 0.045 wt.%, preferably 0.03 wt.%, of the rinsing solution. L-arginine has not only an antibacterial but also an antistatic effect. It is also advantageous if the biofilm inhibitor(s) is urea in a proportion of 1.0 to 3.0 wt.%, preferably 1.0 wt.%, of the rinsing solution. Urea attacks the bacterial cell wall and also has an antistatic effect.It is also particularly advantageous if the rinsing solution contains at least one penetration enhancer from the group consisting of ethanol in a proportion of 7.0 to 20.0 wt.%, a mixture of 1,3-propanediol and propanediol in a total proportion of 0.5 to 5.0 wt.%, and a mixture of Leuconostoc and Radish Root Ferment Filtrate in a total proportion of 0.05 to 0.15 wt.%. The stated proportions are each based on the total rinsing solution and replace a corresponding proportion of the water base. The at least one penetration enhancer improves the penetration of the rinsing solution into the bacteria or other microorganisms in the stated effective concentration ranges and has a general antimicrobial effect. In a preferred embodiment, the or one of the penetration enhancers is ethanol in a proportion of 12.0 to 17.0 wt.%, preferably in a proportion of 15.0 wt.%, of the rinsing solution.As a solvent, ethanol not only enhances penetration but also has defoaming, astringent, degreasing, cleansing, antibacterial, and viscosity-reducing properties, so that ethanol also interacts with the viscosity modulator(s). It is advantageous if the penetration enhancer(s) is a mixture of 1,3-propanediol and propanediol in a total proportion of 1.0 to 5.0 wt.%, preferably in a total proportion of 3.0 wt.%, of the rinsing solution. 1,3-propanediol and propanediol each act individually, and especially as a mixture, as penetration enhancers at the bacterial cell membrane. In an advantageous variant of the rinsing solution, the or one of the penetration enhancers is the mixture of Leuconostoc and Radish Root Ferment Filtrate in a total proportion of 0.05 to 0.09 wt.%, preferably in a total proportion of 0.08 wt.%, of the rinsing solution.This mixture of substances is particularly effective in antibacterial and antiseborrheic properties in the concentration ranges mentioned. To increase the acceptance of the rinsing solution, it is also advantageous if the rinsing solution contains at least one further ingredient from the group consisting of peppermint extract, ginger extract, xylitol glucoside, 1,4-anhydro-D-xylitol, and glucose, with the proportion of each of these further ingredients being less than 0.5% by weight of the rinsing solution. These ingredients essentially enhance the taste and skin compatibility of the rinsing solution and support the effect of all other ingredients of the rinsing solution. Each of the further ingredients replaces a corresponding proportion of the water base in the rinsing solution. The invention is explained in more detail below using examples and the accompanying drawings. The drawings show: Fig.1 shows the absorption spectrum of a photosensitizer contained in a rinsing solution according to the invention in a standardized diagram over the wavelength; Fig. 2 shows the effectiveness of the photosensitizer contained in a rinsing solution from Fig. 1 at different concentrations in a bar chart; and Fig. 3 shows the effectiveness of a rinsing solution according to the invention with the photosensitizer from Fig. 1 compared to bacterial growth with and without rinsing solution or with and without irradiation in a bar chart. According to the present invention, a water-based rinsing solution for photodynamic disinfection, in particular oral disinfection, contains at least one photosensitizer, at least one viscose modulator for adjusting the viscosity of the rinsing solution, at least one biofilm inhibitor and optionally at least one penetration enhancer. The photosensitizer(s) achieve, when irradiated with a radiation source after rinsing, e.g.of the mouth, a mucous membrane, a wound, another natural or surgically created body orifice, a skin surface or an artificial surface with the rinsing solution, the photodynamic disinfection effect by destroying pathogenic bacteria, viruses, fungi, parasites, etc. present there. For example, inside the mouth, bacteria attach themselves to the teeth and gums as a so-called biofilm. The viscose modulator(s) allows a thin film of the rinsing solution to adhere even after rinsing for the subsequent irradiation (e.g. in the mouth, particularly on the teeth, gums and biofilm) by adjusting the viscosity of the rinsing solution. The biofilm inhibitor(s) support the penetration of the rinsing solution into the biofilm or - in general - into microorganisms and pathogens, which is promoted by the optional penetration enhancer(s).The selection and concentrations of the individual ingredients and their relationship to one another significantly determine the effectiveness of the rinse solution for photodynamic oral disinfection. For exceptionally high effectiveness, the photosensitizer(s) from the group consisting of riboflavin 5'-phosphate sodium are present in a proportion of 0.2 to 0.6 wt.% (percent by weight) and one or more photosensitizers other than riboflavin 5'-phosphate sodium are present, each in a proportion of 0.001 to 0.05 wt.%, i.e. either riboflavin 5'-phosphate sodium in the proportion stated for it or at least one other photosensitizer in the proportion stated for the other photosensitizer(s), or both. Furthermore, the viscosity modulator(s) is / are selected from the group consisting of glycerol in a proportion of 1.0 to 5.0% by weight and hyaluronic acid sodium salt in a proportion of 0.01 to 0.3% by weight.are the biofilm inhibitor(s) from the group xylitol in a proportion of 7.0 to 25.0 wt.%, L-arginine in a proportion of 0.01 to 0.5 wt.%, and urea in a proportion of 0.5 to 3.0 wt.%. The remainder of the rinsing solution is a water base, whereby the above-mentioned proportions are each based on the total rinsing solution. The water base can, as is known to the person skilled in the art, be, for example, water, distilled water, or flavored water, or a mixture of water and hydrolate, for example eucalyptus hydrolate or peppermint hydrolate (the latter with the CAS registration number 84082-70-2 according to the Chemical Abstract Service, "CAS," of the American Chemical Society); Alternatively, the water base is an aqueous system to which buffer systems known in the art are added for the purpose of pH stabilization (to a value between 4 and 10, preferably between 5 and 8), for example acids or alkalis including their salts.To improve solubility, protect against demixing, and / or preserve the rinsing solution, other ingredients known in the art can optionally be added to the aqueous system. These ingredients act as buffer systems, preservatives, carrier systems, solubilizers, surfactants, or emulsifiers, and / or promote micelle formation in the rinsing solution. Furthermore, if necessary, the aqueous system can be liposomally encapsulated (for example, with phospholipids or fatty acids) and / or comprise a surfactant-protected or surfactant-free macro-, micro-, or nanoemulsion, the latter two of which have the particularly favorable property of forming in an optically clear state.For the purpose of pH stabilization, improving solubility, protecting against demixing, and / or improving the bioavailability of the rinsing solution, other ingredients known in the art can optionally be added to the surfactant-protected or surfactant-free macro-, micro-, or nanoemulsion, each acting, for example, as a buffer system, preservative, carrier system, solubilizer, surfactant, cosurfactant, and / or emulsifier. The optional penetration enhancer(s) is / are selected from the group consisting of ethanol in a proportion of 7.0 to 20.0 wt.% and / or a mixture of 1,3-propanediol and propanediol in a total proportion of 0.5 to 5.0 wt.% and / or a mixture of Leuconostoc and Radish Root Ferment Filtrate in a total proportion of 0.05 to 0.15 wt.%. The stated proportions of penetration enhancer(s) are based on the total rinsing solution and replace a corresponding proportion of the water base.The effect of at least one photosensitizer during disinfection is as follows: When rinsing the mouth or another body part or surface to be disinfected, the photosensitizer attaches itself to the microorganisms and pathogens (in the mouth: e.g., the biofilm) or penetrates them. The photosensitizer is activated by irradiation. This generates free radicals, e.g., reactive oxygen species (“ROS”), which act as a biocide, i.e., a substance that destroys, for example, fungi (including their spores), bacteria, parasites, and viruses. The wavelength of the irradiation is matched to the photosensitizer used and its absorption spectrum; it generally ranges from the ultraviolet to the infrared range and can be narrowband or broadband. Fig.Figure 1 shows the radiation absorption of a rinsing solution of the aforementioned type containing a single photosensitizer (here: riboflavin 5'-phosphate sodium) when irradiated by a radiation source (here: an LED) with a broadband spectrum B (dotted line in Figure 1), which corresponds to a color temperature of approximately 3000 Kelvin. The absorption spectrum A of the photosensitizer used here (dashed line in Figure 1) has a maximum at a wavelength λ of approximately 445 nm. To activate the photosensitizer, irradiation in the range of this wavelength - or optionally, as in the present example, with a broadband radiation source that also includes this range - is therefore effective. The solid line L shows the actually absorbed radiation; it demonstrates that even at wavelengths well beyond the absorption maximum of the photosensitizer (here, for example,at 600 nm) a certain amount of radiation is still absorbed and, albeit less efficiently, free radicals are formed using the energy of the absorbed radiation. If more than one photosensitizer is used, this generally results in a corresponding number of absorption maxima, to which the radiation source or its radiation spectrum must be adapted. In Fig. 2, based on the aforementioned rinsing solution with riboflavin 5'-phosphate sodium as the only photosensitizer, the effect - in particular the photodynamic effect - on a bacterial suspension of the bacterial species streptococcus mutans ("s. mutans") is shown as an example: The left comparison bar WK shows the number of colony forming units (CFU) of microorganisms (here: s. mutans) per milliliter (CFU / ml) in a growth control measurement in the suspension without treatment with rinsing solution and without irradiation. The corresponding comparison value was approximately 3.2 ∙ 10. 7CFU / ml. The other bars of the diagram show the reduction in the microorganism content when using the (here: only) photosensitizer at various concentrations, including those not according to the invention, in the rinsing solution after effective irradiation for 300 s with between 10 and 45 J / cm², in the present case between 17 and 21 J / cm 2 . At a proportion of 0.01 wt.% of the photosensitizer in the rinsing solution, the microorganism content after irradiation was approximately 2.1 ∙ 10 6 CFU / ml, ie, reduced by more than an order of magnitude (bar R01). The next bar, R25, shows a reduction in the microorganism content to approximately 2.0 ∙ 10 4CFU / ml at a photosensitizer concentration of 0.25 wt% in the rinsing solution, i.e., a reduction of more than 3 orders of magnitude or less than 1 / 1000 of the reference value. As the further bars R50, R125, and R250 show, with increasing photosensitizer concentration from 0.5 wt% (R50), 1.25 wt% (R125), and 2.5 wt% (R250), respectively, the microorganism content increases again, to approximately 1.6 ∙ 10 5 CFU / ml, approx. 1.1 ∙ 10 6 CFU / ml or approx. 2.9 ∙ 10 6CFU / ml. This means that despite a higher concentration of the photosensitizer and the resulting higher number of free radicals, the effectiveness of disinfection decreases. In an optional formulation of the rinsing solution, riboflavin 5'-phosphate sodium is the sole photosensitizer in a proportion of 0.25 to 0.45 wt.%, particularly in a proportion of 0.3 wt.%, of the rinsing solution. Other formulations of the rinsing solution contain, alternatively or in addition to riboflavin 5'-phosphate sodium, one or more other photosensitizers, particularly phycocyanin and / or methylene blue. The proportion of each photosensitizer other than riboflavin 5'-phosphate sodium ("other") is 0.001 to 0.05 wt.%, optionally 0.005 to 0.025 wt.%, of the rinsing solution. Table 1 below lists examples of suitable photosensitizers, each with their identifying CAS registration number: Table 1 The viscosity modulators, at least one of which is contained in the rinsing solution, and their corresponding CAS numbers are listed in Table 2: Table 2 In an optional embodiment, narrower concentration ranges than those listed above are specified for the viscose modulators: For glycerol, a proportion of 2.0 to 3.0 wt.%, preferably a proportion of 2.5 wt.%, and / or for hyaluronic acid sodium salt, a proportion of 0.02 to 0.1 wt.%, preferably a proportion of 0.025 wt.% of the rinsing solution. The biofilm inhibitors can be found in Table 3 below, along with their respective CAS numbers: Table 3: Each of the biofilm inhibitors can also optionally have a narrower concentration range within the concentration ranges specified above. Xylitol is optionally present in the rinse solution in a proportion of 15.0 to 25.0 wt.%, preferably 15.0 wt.%, L-arginine is optionally present in a proportion of 0.01 to 0.045 wt.%, preferably 0.03 wt.%, and urea is optionally present in a proportion of 1.0 to 3.0 wt.%, preferably 1.0 wt.%. Table 4 lists the optional penetration enhancers along with their corresponding CAS numbers: Table 4 In an optional embodiment of the rinsing solution, the penetration enhancers each have a narrower concentration range than their concentration ranges stated above. Ethanol can, for example, be contained in the rinsing solution in a proportion of 12.0 to 17.0 wt.%, preferably in a proportion of 15.0 wt.%, the mixture of 1,3-propanediol and propanediol in a total proportion of 1.0 to 5.0 wt.%, preferably in a total proportion of 3.0 wt.%, and the mixture of Leuconostoc and Radish Root Ferment Filtrate in a total proportion of 0.05 to 0.09 wt.%, preferably in a total proportion of 0.08 wt.%. The two ingredients of the two mentioned mixtures, 1,3-propanediol and propanediol on the one hand andLeuconostoc and Radish Root Ferment Filtrate, on the other hand, have any desired ratio to each other within the respective mixture of substances. Both mixtures are available ready-made, but they can also be added to the rinsing solution in ratios other than those available, in particular up to 100% of one or the other of the two ingredients of the respective mixture. Optionally, further ingredients can be included in the rinsing solution, which primarily serve to improve taste and skin compatibility. The following Table 5 shows some examples of these ingredients, again with the corresponding CAS number (where available) and their respective weight percentages (in wt%). Table 5: Additional ingredients can optionally be added to the water base, which can be assigned to the defined groups of viscosity modulators, biofilm inhibitors, and penetration enhancers, and which support their effectiveness, or ingredients already used in conventional mouthwashes and / or toothpastes known in the art and used for the purpose of protecting tooth enamel or for the care and pain relief of the mucous membrane. It is understood that the proportion of the water base of the rinse solution is reduced by the respective weight proportion of each further (or additional) ingredient contained. Some examples of the rinse solution of the present disclosure are given below. Example 1: The rinse solution according to Example 1 was composed as shown in Table 6 below (weight proportions in wt. %): Table 6 Fig. 3 shows the effect of the rinsing solution according to Example 1 based on two test series. The two bars WK1 and WK2 again show growth control measurements of colony-forming units of the microorganisms in a bacterial suspension (here: again s. mutans): In the first test series, a value of 4.5 × 10 7 CFU / ml (WK1), in the second series of experiments a (similar) value of 4.0 ∙ 10 7 CFU / ml (WK2) were measured. For the first series of experiments, an irradiation control measurement was also carried out after two minutes of incubation in the dark and irradiation as shown in Fig. 2 with a radiation source as shown in Fig. 1 without rinsing solution, which, according to the bar BK in Fig. 3, led to a slight reduction of the measured value to 3.7 ∙ 10 7CFU / ml. Another measurement (bar RK) involved a 1:1 mixing of the bacterial suspension with the rinsing solution according to Example 1, which resulted in a value of 4.3 ∙ 10 7 CFU / ml. Furthermore, for the first series of experiments, two comparative measurements were performed with rinsing solution and irradiation, with the incubation time being 120 seconds and the irradiation time being 300 seconds. The results of these measurements are shown in the bars BES1 and BES2, respectively; the corresponding measured values ​​were 9.0 × 10 1 CFU / ml or 1.1 ∙ 10 2 CFU / ml, i.e., approximately 5.5 orders of magnitude less than the value (WK1 or WK2) of the growth control, or approximately 1 / 500,000. For the comparative second series of experiments, two different conventional mouthwashes (without photodynamic properties) were incubated in the dark for the prescribed 30 seconds; the following measurements yielded values ​​of 1.8 ∙ 10 5CFU / ml (bar SP1) for the first mouthwash or 5.0 ∙ 10 4 CFU / ml (bar SP2) for the second mouthwash. Accordingly, the rinse solution with photodynamic effect according to Example 1 is approximately 1000 times more effective than conventional mouthwashes. Example 2: According to Example 2 and Table 7, an alternative formulation contained (weight percentages in wt.%): Table 7 Example 3: Good results were also achieved with a rinsing solution according to Example 3 or Table 8, which contained additional ingredients mainly to improve the taste (weight percentages in % by weight): Table 8 Example 4: Example 4 contained a simplified formulation according to the following Table 9 (weight percentages in wt%): Table 9 Example 5: Example 5 shows another formulation in Table 10 (weight percentages in wt.%): Table 10 Example 6: Example 6 corresponded to a formulation shown in the following Table 11 (weight percentages in wt%): Table 11 It is understood that the disclosed formulations and weight proportions are subject to manufacturing-related fluctuations or measurement inaccuracies, the magnitude of which depends in particular on the manufacturing or measurement methods used. Thus, depending on the method, deviations from the stated weight proportions in the range of typically up to + / -10% of the stated weight proportions (not of the entire rinsing solution) are possible and included. The invention is not limited to the illustrated and described embodiments, but encompasses those variants, modifications, and combinations thereof that fall within the scope of the appended claims.

Claims

Claims:

1. Rinsing solution for photodynamic disinfection, in particular oral disinfection, containing, in each case based on the total rinsing solution, at least one photosensitizer from the group consisting of riboflavin 5'-phosphate sodium in a proportion of 0.2 to 0.6 wt.% and a photosensitizer other than riboflavin 5'-phosphate sodium in a proportion of 0.001 to 0.05 wt.%, at least one viscosity modulator from the group consisting of glycerol in a proportion of 1.0 to 5.0 wt.% and hyaluronic acid sodium salt in a proportion of 0.01 to 0.3 wt.%, at least one biofilm inhibitor from the group consisting of xylitol in a proportion of 7.0 to 25.0 wt.%, L-arginine in a proportion of 0.01 to 0.5 wt.% and urea in a proportion of 0.5 to 3.0 wt.%, and the remainder being water-based.

2. Rinsing solution according to claim 1, wherein the or one of the photosensitizer(s) riboflavin 5'-phosphate sodium is present in a proportion of 0.25 to 0.45 wt.%, preferably in a proportion of 0.3 wt.%, of the rinsing solution.

3. Rinsing solution according to claim 1 or 2, wherein the photosensitizer(s) phycocyanin is present in the stated proportion of 0.001 to 0.05 wt.%, preferably in a proportion of 0.005 to 0.025 wt.%, of the rinsing solution.

4. Rinsing solution according to any one of claims 1 to 3, wherein the photosensitizer(s) methylene blue is present in the stated proportion of 0.001 to 0.05 wt.%, preferably in a proportion of 0.005 to 0.025 wt.%, of the rinsing solution.

5. Rinsing solution according to any one of claims 1 to 4, wherein the viscosity modulator(s) glycerol is present in a proportion of 2.0 to 3.0 wt.%, preferably in a proportion of 2.5 wt.%, of the rinsing solution.

6. Rinsing solution according to any one of claims 1 to 5, wherein the or one of the viscosity modulator(s) is sodium hyaluronate. Salt in a proportion of 0.02 to 0.1 wt.%, preferably in a proportion of 0.025 wt.%, of the rinsing solution.

7. Rinsing solution according to any one of claims 1 to 6, wherein the biofilm inhibitor(s) xylitol is present in a proportion of 15.0 to 25.0 wt.%, preferably in a proportion of 15.0 wt.%, of the rinsing solution.

8. Rinsing solution according to any one of claims 1 to 7, wherein the biofilm inhibitor(s) L-arginine is present in a proportion of 0.01 to 0.045 wt.%, preferably in a proportion of 0.03 wt.%, of the rinsing solution.

9. Rinsing solution according to any one of claims 1 to 8, wherein the biofilm inhibitor(s) urea is present in a proportion of 1.0 to 3.0 wt.%, preferably in a proportion of 1.0 wt.%, of the rinsing solution.

10. Rinsing solution according to any one of claims 1 to 9, further comprising at least one penetration enhancer from the group ethanol in a proportion of 7.0 to 20.0 wt.%, a mixture of 1,3-propanediol and propanediol in a total proportion of 0.5 to 5.0 wt.%.-% and a mixture of leuconostoc and radish root ferment filtrate in a total proportion of 0.05 to 0.15 wt.%, wherein the aforementioned proportions are based on the total rinsing solution and replace a corresponding proportion of the water base.

11. Rinsing solution according to claim 10, wherein the penetration enhancer or one of the penetration enhancers is ethanol in a proportion of 12.0 to 17.0 wt.%, preferably in a proportion of 15.0 wt.%, of the rinsing solution.

12. Rinsing solution according to claim 10 or 11, wherein the penetration enhancer or one of the penetration enhancers is the mixture of 1,3-propanediol and propanediol in a total proportion of 1.0 to 5.0 wt.%, preferably in a total proportion of 3.0 wt.%, of the rinsing solution.

13. Rinsing solution according to one of claims 10 to 12, wherein the penetration enhancer or one of the penetration enhancers in the mixture of Leuconostoc and Radish Root Ferment Filtrate in an entire. A proportion of 0.05 to 0.09 wt.%, preferably in a total proportion of 0.08 wt.%, of the rinsing solution.

14. Rinsing solution according to any one of claims 1 to 13, further comprising at least one additional ingredient from the group consisting of peppermint extract, ginger extract, xylityl glucoside, 1,4-anhydro-D-xylitol and glucose, wherein the proportion of each of these additional ingredients is less than 0.5 wt.% of the rinsing solution and replaces a corresponding proportion of the water base.